Materiały źródłowe

• #1 Radiation Enteropathy – Pathogenesis, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4346191/

  The main clinical features of delayed radiation enteropathy are altered intestinal transit, malabsorption, and dysmotility. […] Delayed radiation enteropathy is a chronic, often progressive disorder and associated with substantial long-term morbidity. […] The classical understanding of intestinal radiation toxicity was based entirely on the target cell theory. […] The severity of epithelial injury was the only determinant of early pathology, while a different, more slowly proliferating target cell (fibroblast, endothelial cell) was used to explain delayed effects. […] Hence, the contemporary view is that many tissues and cell types in the gut participate and contribute to injury. […] The intestinal microvasculature is recognized as an important contributor to radiation toxicity of the bowel.

• #1 Pathology and Pathogenesis of Radiation Bowel Disease: Histopathological Appraisal in the Clinical Setting – European Medical Journal

  https://www.emjreviews.com/gastroenterology/article/pathology-and-pathogenesis-of-radiation-bowel-disease-histopathological-appraisal-in-the-clinical-setting/

  RBD results from therapy-induced damage to surrounding non-cancerous tissues, which leads to changes in the normal physiological functions of the various organs, including the small and large bowel. […] The initial stages of RBD involve damage to the epithelial tissue, a process that triggers an inflammatory response. For those patients who go on to develop RBD, this process will be followed by progressive ischaemia and fibrosis. […] Cells exposed to ionising radiation experience oxidative stress injuries. The damage is widespread; however, the principal subcellular target is the nuclear DNA. […] Both direct and indirect mechanisms inhibit DNA from fulfilling its function as a template for DNA transcription. The nuclear chromatin is directly targeted, causing DNA damage through the generation of inter and intra-strand cross-linkages, breaks, and mutations.

• #1 Radiation Enteritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK526032/

  Radiation enteritis is damage to the small and/or large intestines secondary to radiation. Different terms like radiation colitis, radiation enteropathy, radiation mucositis, and pelvic radiation disease have been used to describe this phenomenon. Radiation proctitis is a different term that is used to describe the involvement of the rectum and sigmoid colon. Radiotherapy is used as a treatment for many cancers. Radiation enteritis can be acute or chronic. The chronic form usually develops between 3 months to 30 years after treatment. […] Radiation enteritis is an unavoidable side effect of radiotherapy, although its development is highly variable, depending on the duration, dosage, and gut sensitivity to radiation. […] The repetitive injuries caused to the intestinal mucosa by ionizing radiation, as well as its complex mechanism of healing, are proposed to cause radiation enteritis. Exposure of normal tissues to radiation leads to the production of reactive ions that combine with intracellular water molecules to form radicals like hydroxyl and other free radicals. These radicals are deemed responsible for causing breaks in DNA and causing cell death. Secondary to radiation exposure, activation of genes that are responsible for the translation of transforming growth factor (TGF-beta) takes place. This activation stimulates collagen and fibronectin genes promoting fibrosis. Tissues with rapid proliferation are sensitive to radiation, and thus, cell membrane disruption is also responsible for the cell death observed. The epithelial cells of the small intestine are more radiosensitive as compared to the colon and rectum. Studies show that the presence of Bcl2 in the rectum is the reason for this discrimination. The most characteristic pathologic changes observed are fibrosis and obliterative endarteritis in the intestinal epithelium.

• #1 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  Histopathologic findings in acute radiation-related intestinal damage include the following characteristics: […] In addition, mitotic arrest, karyorrhexis, and lysis of the crypt and deep epithelial cells are observed. If the submucosal damage is not prominent, the epithelial cells regenerate and the changes regress. Conversely, severe submucosal changes lead to progression of mucosal injury, ulcerations, and erosion of the villi. The histologic findings in the acute phase correlate poorly with clinical symptoms, but amounts of malabsorption vary because of the mucosal damage. […] Histologically, obliterative endarteritis of the small vessels in the intestinal wall characterizes chronic radiation injury to the intestine. Associated lymphoid atrophy, lymphatic dilation, and fibrosis of the submucosal tissue are observed. The progressive vascular sclerosis leads to chronic ischemia of the overlying tissue, ultimately resulting in mucosal atrophy. Scar tissue replaces the submucosal tissue, resulting in further decrease in vascularity and contracture of the intestinal wall. Chronic mucosal ulceration may result in fistula formation and hemorrhage.

• #1 Raneen Omary. Contents Definition Pathogenesis Epidemiology Acute Radiation Enteritis Chronic Radiation Enteritis Risk Factors Diagnosis DD Medical Management. – ppt download

  https://slideplayer.com/slide/6616433/

  Pathogenesis Cells with a high proliferative rate, such as the gastrointestinal epithelium, are susceptible to injury from radiation The primary effect of radiation is on mucosal stem cells within the crypts of Lieberkuhn Inflammation, edema, shortening of villi (small absorption area) Histological changes within hours Inflammation, abbcess- 2-4 weeks. […] Subsequent Changes: – Vasculitis – Fibrosis (submucosa) – Thickening of the small intestine (ischemia, lymphatic damage) – Also: ulceration perforation, fistula, abcess./Fibrosis, stricture, obstruction – Absorption of fats, carbohydrates, protein, bile salts, B12 vitamin. […] Chronic radiation enteritis is due to an obliterative arteritis that leads to intestinal ischemia, which can result in stricture, ulceration, fibrosis and occasionally fistula formation.

• #1 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  The imbalance of intestinal flora homeostasis disrupts the integrity of the intestinal epithelial barrier. […] Therefore, when ISCs are damaged, the proliferation of epithelial cells cannot supplement the death of epithelial cells in time, resulting in shortened villi, which subsequently reduces the intestinal surface area and intestinal absorption function. […] Researchers have found that the levels of claudin-2, claudin-3, claudin-4, claudin-10, JAM-1, and occludin are changed in the radiation group, which disturbs the epithelial barrier and increases intestinal permeability. […] The treatment of RIII is basically symptomatic and nutritional support treatment, such as anti-diarrhea, anti-vomiting, anti-inflammation, and surgical treatment, and an ideal means of prevention and treatment is lacking.

• #1 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  The intestinal mucosal epithelial cells, together with the basement membrane, constitute the intestinal epithelial mechanical barrier. […] However, the epithelium of the small intestine renews very quickly and is extremely sensitive to radiation, which disrupts its integrity. […] Radiation can cause DNA damage to intestinal epithelial cells via direct or indirect means, leading to cell death and tight junction damage, which subsequently disrupt the integrity of the intestinal mechanical barrier. […] After exposure to ionizing radiation, the main death mode of intestinal epithelial cells is apoptosis. […] Studies have shown that p53 plays an important role in radiation response after intestinal injury. […] In addition to apoptosis, recent studies have shown that autophagy, pyroptosis, and ferroptosis are also involved in radiation-induced intestinal epithelial injury.

• #1 In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury | Scientific Reports

  https://www.nature.com/articles/srep15738

  The pathophysiological mechanism involved in side effects of radiation therapy and especially the role of the endothelium remains unclear. […] This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. […] The concept that the microvasculature plays a central role in the radiation toxicity of many tissues, including the intestine, is often described, but lacks robust demonstration. […] Irradiation leads to endothelial cell apoptosis, increased vascular permeability and acquisition of a pro-inflammatory and pro-coagulant phenotype. […] We previously showed that PAI-1 total knockout mice are protected against radiation enteritis, but there was no evidence that this was dependent on the PAI-1 endothelial pool.

• #1 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  Radiation damages vascular endothelial cells in various ways, resulting in endothelial cell swelling, increased permeability, inflammatory cell adhesion and migration, and microthrombosis in microvessels. […] The senescence of endothelial cells results in a senescence-related secretory phenotype in which endothelial cells secrete cytokines, proteins, and other factors that cause dysfunction in neighboring cells or contribute to a chronic inflammatory state. […] The intestinal immune system plays a pivotal role in the maintenance of intestinal homeostasis, and its imbalance is closely related to intestinal diseases. […] In RIII, the levels of immune cells and immune cytokines changed, suggesting an important role of immune imbalance in RIII. […] There is evidence that the pathophysiology of RIII is correlated with intestinal microbiota dysregulation.

• #1 Radiation colitis – Wikipedia

  https://en.wikipedia.org/wiki/Radiation_colitis

  Through its strong fibrogenic and proinflammatory effects, TGF- also plays a significant role in the pathogenesis of chronic radiation colitis. […] TGF- levels in irradiated tissues are significantly higher and stay elevated in smooth muscle cells, vascular endothelial cells, and fibrocytes for up to 26 weeks.

• #1 (PDF) REVIEW ARTICLE ON RADIATION-INDUCED PROCTITIS & ENTERITIS

  https://www.academia.edu/84046040/REVIEW_ARTICLE_ON_RADIATION_INDUCED_PROCTITIS_and_ENTERITIS

  The hyperstimulation of transforming growth factor 1 (TGF-1) leads to increased fibrosis and, ultimately, organ failure. […] Radiation enteritis and other radiation-induced, long-term complications are characterized by excessive stimulation of TGF-1. […] The manifestations of late radiation enteropathy are primarily due to changes in compartments other than the mucosa, such as intestinal wall fibrosis and obliterating vascular sclerosis. […] The present paper summarizes clinical, pathophysiologic, and radiobiologic aspects pertinent to the development of chronic intestinal radiation injury.

• #1 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  There is also evidence supporting a pivotal role for gut microbiota dysbiosis in the development of radiation-induced bowel injury. […] Radiation injury to the small and large bowel is due to damage to the lipid layer of the cell membrane, proteins, and cellular DNA. The effects are most marked in tissues containing cells with a high mitotic rate. […] The degree of intestinal injury is directly related to the total radiation dose, the fractionation, and the distribution of the dose in tissues peripheral to the target area. Early in the evolution of RT, large single radiation doses were noted to cause severe or even lethal adverse effects; the same cumulative dose given as small fractions over the course of several days or weeks was better tolerated. […] Excessive exposure of adjacent normal tissue to radiation also contributes to the development of radiation-induced enteropathy. Current techniques allow for a focused delivery of radiation energy to the target tissues with intracavitary radiation as well as external beam with supervoltage radiation, multiple portals, and the improved shielding of adjacent normal structures.

• #1 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. […] Radiation enteritis is caused by the dynamic interaction of intestinal microbiome changes, epithelial cell injury and repair, endothelial cell injury and remodeling, fibroplasia, and enteric nervous system changes. The basic pathological changes include two aspects: intestinal mucosal injury caused by radiation and vascular connective tissue injury caused by radiation vascular endothelial cells.

• #1 The impact of pelvic radiotherapy on the gut microbiome and its role in radiation-induced diarrhoea: a systematic review | Radiation Oncology | Full Text

  https://ro-journal.biomedcentral.com/articles/10.1186/s13014-021-01899-y

  The human gut microbiota can be classified at the phylum level into Bacteroidetes, Actinobacteria, Proteobacteria, Fusobacteria, Firmicutes, and unclassified phyla. Only five of the studies included in our review reported significant phylum-level changes in microbial composition before and after pelvic radiotherapy, although these results were inconsistent. Overall, the consensus observation is a significant increase in Proteobacteria, unclassified bacteria, and Fusobacteria and a significant decrease in Firmicutes and Bacteroidetes in response to pelvic radiotherapy. The phylum diversity in the gut is clearly remodelled after pelvic radiotherapy. […] Pelvic radiotherapy clearly kills beneficial intestinal anaerobic bacteria, such as Faecalibacterium, Peptostreptococcus, Lactobacillus, and Roseburia. This significant proportion of the microbiome is less likely to reappear following diarrhoea induced by pelvic radiotherapy. Therefore, probiotic supplementation may reduce the occurrence of diarrhoea in response to pelvic radiotherapy.

• #1

  https://journals.lww.com/ajg/fulltext/2014/10002/improvement_of_chronic_diarrhea_associated_with.1347.aspx

  Radiation enteritis is a well-described complication of pelvic or abdominal radiation therapy. […] The most common mechanism to explain diarrhea in chronic radiation enteritis is bile acid malabsorption. Excess bile salts in the colon stimulate water secretion, leading to increased motility and diarrhea. […] Cholestyramine irreversibly binds bile salts, thus acting as a surrogate ileum and preventing concomitant electrolyte and water secretion into the colon.

• #1 Radiation-Induced Enteritis: Incidence, Mechanisms, and Management

  https://www.cancernetwork.com/view/radiation-induced-enteritis-incidence-mechanisms-and-management

  Radiation-induced diarrhea can be severe and life threatening. It is obvious that by reducing the chemoradiation-induced bowel symptoms, the patients quality of life during (and following) therapy can be enhanced. Additionally, minimizing the severity of radiation-induced enteritis may increase the probability of completing the planned treatment without interruption and improve the outcome. It is also expected that effective management/prevention of severe diarrhea would avoid hospitalization for complications such as dehydration, fluid and electrolyte imbalance, or nutritional decline. […] The pathophysiology of radiation enteritis is not well understood. Radiation-induced mucosal damage results in decreased absorption of water and electrolytes, causing diarrhea. Another possible mechanism is decreased bile acid absorption in the ileum (due to mucosal damage). When passing through the bowel, the excess bile acid irritates and damages the protective mucosal cap of the intestine. This results in transudation of fluid and electrolytes into the lumen and causes diarrhea. […] Conventional antidiarrheal agents fail to prevent the onset of grade 3/4 diarrhea.

• #1 Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice – ADS

  https://ui.adsabs.harvard.edu/abs/2022JRadR..63..213L/abstract

  Patients receiving pelvic or abdominal radiotherapy may experience acute and/or chronic side effects due to gastrointestinal changes. […] In this study, we found that Liriodendrin can reduce the expression of Cer, Cer1P and S1P in the sphingolipid pathway, thereby reducing the histological damage to the intestinal tract of mice and inhibiting the apoptosis of intestinal tissue cells. […] Liriodendrin can reduce the levels of pro-inflammatory cytokines (IL-6 and TNF-), and it is suggested through flow cytometry that the proportion of neutrophils in the intestinal tissue can decrease due to the existence of Liriodendrin. […] The western blot evaluation revealed that Liriodendrin significantly inhibited the activation of Bcl-2/Bax/Caspase-3 and NF-B signaling pathways. […] The results show that Liriodendrin can inhibit intestinal inflammation and intestinal cell apoptosis through the sphingolipid pathway. […] Therefore, the aforementioned results demonstrated that Liriodendrin may be a promising drug for the treatment of radiation enteritis.

• #1 Family

  https://patents.google.com/patent/ES2538478T3/en

  Rifaximina jest szczególnie korzystna, ponieważ nie jest wchłaniana i nie powoduje zakłócenia normalnej flory (szczególnie jelita cienkiego), co predysponuje pacjentów do nadmiernego wzrostu bakterii patogennych, a leczenie rifaksyminą może leczyć i zapobiegać temu nadmiernemu wzrostowi bakterii. […] Mechanizm biegunki wywołanej promieniowaniem obejmuje ostre uszkodzenie mechaniczne komórek krypt nabłonka przewodu pokarmowego. […] Uszkodzenie tego typu prowadzi do śmierci komórki (czy to przez mechanizm martwiczy, czy apoptyczny), zapalenie i owrzodzenie błony śluzowej jelit, które następnie jest narażone na drażniące sole żółciowe i staje się podatne na infekcje oportunistyczne. […] W przypadku ciężkich przypadków może wystąpić ostra niedrożność jelit, przetoki lub perforacja jelit.

• #1 Radiation Enteropathy – Pathogenesis, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4346191/

  Early radiation enteropathy occurs within 3 months of radiation therapy and affects the quality of life at the time of treatment. […] Delayed intestinal radiation toxicity is a highly important issue for long term cancer survivors. […] The aim of the review is to provide an introduction of the subject tailored to the needs of the gastroenterologist. […] The incidence and severity of intestinal radiation toxicity depend on a number of therapy-related and patient-related factors. […] Intestinal radiation toxicity (radiation enteropathy) is generally classified as early (acute) when it occurs within 3 months of radiation therapy, or delayed (chronic) when it occurs more than 3 months after radiation therapy. […] The pathogenesis of delayed radiation enteropathy is complex and involves changes in most compartments of the intestinal wall.

• #1 (PDF) REVIEW ARTICLE ON RADIATION-INDUCED PROCTITIS & ENTERITIS

  https://www.academia.edu/84046040/REVIEW_ARTICLE_ON_RADIATION_INDUCED_PROCTITIS_and_ENTERITIS

  Radiation enteritis is becoming more common as more cancer patients receive radiotherapy and their long-term survival improves. […] Chronic radiation enteritis is documented in up to 20% of pelvic radiotherapy patients, however, this may underestimate its true frequency because not all patients with gastrointestinal symptoms following radiotherapy seek medical attention. […] Low body mass index, abdominal surgery, and co-morbid disorders predispose to chronic radiation enteritis. […] Radiation dose, fractionation, method, and chemotherapy may also play a role. […] Chronic radiation enteritis has many clinical characteristics because it can affect any GI organ. […] Recent progress in molecular biology has shed some light on the pathogenesis of radiation enteritis and other diseases that are characterized by excessive fibrosis.

• #1 Radiation enteropathy – Wikipedia

  https://en.wikipedia.org/wiki/Radiation_enteropathy

  Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer. […] Early radiation enteropathy is very common during or immediately after the course of radiotherapy. This involves cell death, mucosal inflammation and epithelial barrier dysfunction. This injury is termed mucositis and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain. […] The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes intestinal epithelial mucosal atrophy, vascular sclerosis, and progressive fibrosis of the intestinal wall, among other changes in intestinal neuroendocrine and immune cells and in the gut microbiota. These changes may produce dysmotility, strictures, malabsorption and bleeding. Problems in the terminal ileum and rectum predominate.

• #1 Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats | BMC Complementary Medicine and Therapies | Full Text

  https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-025-04820-2

  Following the administration of CKI, expression of CB1 and Inflammatory factors was found to be decreased in rats compared with that in the radiotherapy model group. This effect was also observed following the administration of the CB1 agonist, while the administration of the CB1 inhibitor attenuated the effect of CKI. […] CKI treatment significantly reduced the pro-inflammatory factors and the expression of p38 MAPK signaling pathway-related proteins in the ileum of rats with RE, indicating that CKI can improve the inflammatory response and inhibit the activation of p38 MAPK signaling. […] Therefore, it can be hypothesised that CKI may improve radiation enteritis by mediating CB1 to inhibit the p38 MAPK pathway.

• #1 Radiation Enteropathy – Pathogenesis, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4346191/

  There has been only modest change in cancer incidence and mortality during the past several decades, but the number of cancer survivors has almost tripled during the same period. […] Many cancer survivors have undergone radiation therapy of tumors in the pelvis or abdomen, thus rendering the bowel at risk for injury. […] Significant progress toward reducing toxicity of radiation therapy has been made by the introduction of so-called dose-sculpting treatment techniques, which allow more precise delivery of the radiation beam. […] Moreover, new insight into the underlying pathophysiology have resulted in an improved understanding of mechanisms of radiation-induced bowel toxicity and in development of new diagnostic strategies and management opportunities. […] This article discusses the pathogenesis of early and delayed radiation-induced bowel toxicity, reviews current management options, and outlines priorities for future research.

• #2 Radiation Enteropathy – Pathogenesis, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4346191/

  In other words, we have progressed beyond the single target cell concept and now recognize that, in addition to epithelial injury, the intestinal microvasculature, immune mechanisms, neuro-immune interactions, the intestinal microbiome, the composition of the intraluminal contents, and a host of other factors play important roles. […] The recognition that delayed radiation injury may develop in the wake of severe acute injury was recognized clinically by Bourne and colleagues and subsequently coined consequential late effects by Peters. […] However, it became increasingly clear that the terminology failed to recognize the complexity of radiation effects in multicellular tissues and organs. […] The complexity of radiation enteropathy requires re-thinking of some of the old dogmas, but opens up the field for development of exciting new therapeutic strategies. […] As an IBD model, radiation enteropathy offers substantial advantages in terms of methods and clinical relevance. […] The pathogenesis of radiation enteropathy is multifactorial and far more complex than previously assumed the traditional target cell concept is largely obsolete.

• #2 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  Radiation-induced intestinal injury (RIII) is one of the most common intestinal complications caused by radiotherapy for pelvic and abdominal tumors and it seriously affects the quality of life of patients. […] Ionizing radiation acts on the body and can cause direct and indirect damage. On the one hand, ionizing radiation directly transfers energy to the body’s biological macromolecules, such as DNA, RNA, and proteins. On the other hand, it ionizes water and produces free radicals, such as superoxide anions (O2−), hydrogen peroxide (H2O2), and hydroxyl radicals (OH−), which interact with biological macromolecules and cause damage to the body. […] Excessive ionizing radiation exposure can lead to the destruction of biological macromolecules, which causes damage to the intestinal epithelial barrier and intestinal vascular endothelial cells and affect intestinal immunity and intestinal microorganisms, resulting in local inflammation, mucosal edema, bleeding and coagulation disorders, bacterial infection, and even death.

• #2 Research progress on the mechanism of radiation enteritis

  https://ouci.dntb.gov.ua/en/works/7BABnWg9/

  Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. […] The underlying mechanisms of Re are complex and have not yet been elucidated. The purpose of this review is to provide an overview of the pathogenesis of Re. We reviewed the role of intestinal epithelial cells, intestinal stem cells (ISCs), vascular endothelial cells (ECs), intestinal microflora, and other mediators of Re, noting that a better understanding of the pathogenesis of Re may lead to better treatment modalities. […] Severe acute and chronic radiation enteritis result from the damage to the crypt-based intestinal stem cells and their derivatives, which include the Paneth cells. Paneth cells regulate the proliferation and differentiation of the intestinal stem cells. The effect of ionizing radiation on the intestinal stem cells and its derivatives, and the knowledge can be used to develop effective treatment of radiation enteritis is discussed.

• #2 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  The intestinal mucosal epithelial cells, together with the basement membrane, constitute the intestinal epithelial mechanical barrier. […] However, the epithelium of the small intestine renews very quickly and is extremely sensitive to radiation, which disrupts its integrity. […] Radiation can cause DNA damage to intestinal epithelial cells via direct or indirect means, leading to cell death and tight junction damage, which subsequently disrupt the integrity of the intestinal mechanical barrier. […] After exposure to ionizing radiation, the main death mode of intestinal epithelial cells is apoptosis. […] Studies have shown that p53 plays an important role in radiation response after intestinal injury. […] In addition to apoptosis, recent studies have shown that autophagy, pyroptosis, and ferroptosis are also involved in radiation-induced intestinal epithelial injury.

• #2 In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury | Scientific Reports

  https://www.nature.com/articles/srep15738

  The pathophysiological mechanism involved in side effects of radiation therapy and especially the role of the endothelium remains unclear. […] This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. […] The concept that the microvasculature plays a central role in the radiation toxicity of many tissues, including the intestine, is often described, but lacks robust demonstration. […] Irradiation leads to endothelial cell apoptosis, increased vascular permeability and acquisition of a pro-inflammatory and pro-coagulant phenotype. […] We previously showed that PAI-1 total knockout mice are protected against radiation enteritis, but there was no evidence that this was dependent on the PAI-1 endothelial pool.

• #2 Diagnosis and management of chronic radiation enteritis – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-management-of-chronic-radiation-enteritis/print

  Injury to the intestines can occur following radiation therapy for cancer. It usually develops three or more months after radiation therapy. Chronic radiation enteritis is due to an obliterative arteritis that leads to intestinal ischemia, which can result in stricture, ulceration, fibrosis, and occasionally fistula formation. The physiologic consequences can include altered intestinal transit, reduced bile acid absorption, increased intestinal permeability, bacterial overgrowth, and lactose malabsorption. […] The pathogenesis, clinical manifestations, and risk factors for chronic radiation enteritis and other radiation-related gastrointestinal toxicities are discussed separately. […] The diagnosis of chronic radiation enteritis is suspected in patients with nausea, vomiting, abdominal pain, diarrhea, or lower gastrointestinal bleeding three or more months after completion of radiation therapy.

• #2 (PDF) REVIEW ARTICLE ON RADIATION-INDUCED PROCTITIS & ENTERITIS

  https://www.academia.edu/84046040/REVIEW_ARTICLE_ON_RADIATION_INDUCED_PROCTITIS_and_ENTERITIS

  The hyperstimulation of transforming growth factor 1 (TGF-1) leads to increased fibrosis and, ultimately, organ failure. […] Radiation enteritis and other radiation-induced, long-term complications are characterized by excessive stimulation of TGF-1. […] The manifestations of late radiation enteropathy are primarily due to changes in compartments other than the mucosa, such as intestinal wall fibrosis and obliterating vascular sclerosis. […] The present paper summarizes clinical, pathophysiologic, and radiobiologic aspects pertinent to the development of chronic intestinal radiation injury.

• #2 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. […] Radiation enteritis is caused by the dynamic interaction of intestinal microbiome changes, epithelial cell injury and repair, endothelial cell injury and remodeling, fibroplasia, and enteric nervous system changes. The basic pathological changes include two aspects: intestinal mucosal injury caused by radiation and vascular connective tissue injury caused by radiation vascular endothelial cells.

• #2 Radiation-Induced Enteritis: Incidence, Mechanisms, and Management

  https://www.cancernetwork.com/view/radiation-induced-enteritis-incidence-mechanisms-and-management

  Radiation-induced diarrhea can be severe and life threatening. It is obvious that by reducing the chemoradiation-induced bowel symptoms, the patients quality of life during (and following) therapy can be enhanced. Additionally, minimizing the severity of radiation-induced enteritis may increase the probability of completing the planned treatment without interruption and improve the outcome. It is also expected that effective management/prevention of severe diarrhea would avoid hospitalization for complications such as dehydration, fluid and electrolyte imbalance, or nutritional decline. […] The pathophysiology of radiation enteritis is not well understood. Radiation-induced mucosal damage results in decreased absorption of water and electrolytes, causing diarrhea. Another possible mechanism is decreased bile acid absorption in the ileum (due to mucosal damage). When passing through the bowel, the excess bile acid irritates and damages the protective mucosal cap of the intestine. This results in transudation of fluid and electrolytes into the lumen and causes diarrhea. […] Conventional antidiarrheal agents fail to prevent the onset of grade 3/4 diarrhea.

• #2 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  Radiation damages vascular endothelial cells in various ways, resulting in endothelial cell swelling, increased permeability, inflammatory cell adhesion and migration, and microthrombosis in microvessels. […] The senescence of endothelial cells results in a senescence-related secretory phenotype in which endothelial cells secrete cytokines, proteins, and other factors that cause dysfunction in neighboring cells or contribute to a chronic inflammatory state. […] The intestinal immune system plays a pivotal role in the maintenance of intestinal homeostasis, and its imbalance is closely related to intestinal diseases. […] In RIII, the levels of immune cells and immune cytokines changed, suggesting an important role of immune imbalance in RIII. […] There is evidence that the pathophysiology of RIII is correlated with intestinal microbiota dysregulation.

• #2 radiation enteritis

  https://www.aboutcancer.com/radiation_enteritis_utd_807.htm

  Chronic radiation enteritis usually develops only after large doses of radiation therapy have been delivered (4500 to 5500 cGY); it is uncommon at lower doses. […] Intestinal injury is believed to be related to oxidative damage caused by the formation of free radicals. The end result is an obliterative endarteritis that leads to intestinal ischemia resulting in stricturing with ulceration and fibrosis and occasionally fistula formation. […] The precise mechanisms leading from oxidative damage to the histologic and morphologic abnormalities described above are incompletely understood. Several theories have been proposed, all of which are probably interrelated: […] One model suggests that fibrosis develops from the initial mucosal injury […] Another theory suggests that fibrosis develops in connective tissues where radiation has caused a decrease in cell turnover and a low rate of proliferation.

• #2 (PDF) REVIEW ARTICLE ON RADIATION-INDUCED PROCTITIS & ENTERITIS

  https://www.academia.edu/84046040/REVIEW_ARTICLE_ON_RADIATION_INDUCED_PROCTITIS_and_ENTERITIS

  Radiation enteritis is becoming more common as more cancer patients receive radiotherapy and their long-term survival improves. […] Chronic radiation enteritis is documented in up to 20% of pelvic radiotherapy patients, however, this may underestimate its true frequency because not all patients with gastrointestinal symptoms following radiotherapy seek medical attention. […] Low body mass index, abdominal surgery, and co-morbid disorders predispose to chronic radiation enteritis. […] Radiation dose, fractionation, method, and chemotherapy may also play a role. […] Chronic radiation enteritis has many clinical characteristics because it can affect any GI organ. […] Recent progress in molecular biology has shed some light on the pathogenesis of radiation enteritis and other diseases that are characterized by excessive fibrosis.

• #2 Radiation enteropathy – Wikipedia

  https://en.wikipedia.org/wiki/Radiation_enteropathy

  Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer. […] Early radiation enteropathy is very common during or immediately after the course of radiotherapy. This involves cell death, mucosal inflammation and epithelial barrier dysfunction. This injury is termed mucositis and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain. […] The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes intestinal epithelial mucosal atrophy, vascular sclerosis, and progressive fibrosis of the intestinal wall, among other changes in intestinal neuroendocrine and immune cells and in the gut microbiota. These changes may produce dysmotility, strictures, malabsorption and bleeding. Problems in the terminal ileum and rectum predominate.

• #2 Radiation Enteropathy – Pathogenesis, Treatment, and Prevention

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4346191/

  The main clinical features of delayed radiation enteropathy are altered intestinal transit, malabsorption, and dysmotility. […] Delayed radiation enteropathy is a chronic, often progressive disorder and associated with substantial long-term morbidity. […] The classical understanding of intestinal radiation toxicity was based entirely on the target cell theory. […] The severity of epithelial injury was the only determinant of early pathology, while a different, more slowly proliferating target cell (fibroblast, endothelial cell) was used to explain delayed effects. […] Hence, the contemporary view is that many tissues and cell types in the gut participate and contribute to injury. […] The intestinal microvasculature is recognized as an important contributor to radiation toxicity of the bowel.

• #2 Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats | BMC Complementary Medicine and Therapies | Full Text

  https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-025-04820-2

  Following the administration of CKI, expression of CB1 and Inflammatory factors was found to be decreased in rats compared with that in the radiotherapy model group. This effect was also observed following the administration of the CB1 agonist, while the administration of the CB1 inhibitor attenuated the effect of CKI. […] CKI treatment significantly reduced the pro-inflammatory factors and the expression of p38 MAPK signaling pathway-related proteins in the ileum of rats with RE, indicating that CKI can improve the inflammatory response and inhibit the activation of p38 MAPK signaling. […] Therefore, it can be hypothesised that CKI may improve radiation enteritis by mediating CB1 to inhibit the p38 MAPK pathway.

• #2 Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice. | EBSCOhost

  https://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=04493060&AN=156007047&h=MclqldONEiD4AwNJwgVZhfl5EHuPYOkMhBV8J1AXCq3mjsnwkkeuC%2FK38GPorMleTpyYtniqGrMQAHAS3o1Crg%3D%3D&crl=f

  Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice. […] In this study, we found that Liriodendrin can reduce the expression of Cer, Cer1P and S1P in the sphingolipid pathway, thereby reducing the histological damage to the intestinal tract of mice and inhibiting the apoptosis of intestinal tissue cells. […] The results show that Liriodendrin can inhibit intestinal inflammation and intestinal cell apoptosis through the sphingolipid pathway. Therefore, the aforementioned results demonstrated that Liriodendrin may be a promising drug for the treatment of radiation enteritis.

• #2 In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury | Scientific Reports

  https://www.nature.com/articles/srep15738

  Here, we show that irradiation very rapidly induces fibrin deposition. […] We showed that conditional endothelium-specific PAI-1 deletion limits radiation-induced macrophage infiltration (CD68+ cells) in the radiation acute phase. […] We demonstrate in this work that PAI-1 plays a role in the initiation of radiation-induced intestinal injury by an endothelium-dependent mechanism.

• #2 Pathology and Pathogenesis of Radiation Bowel Disease: Histopathological Appraisal in the Clinical Setting – European Medical Journal

  https://www.emjreviews.com/gastroenterology/article/pathology-and-pathogenesis-of-radiation-bowel-disease-histopathological-appraisal-in-the-clinical-setting/

  RBD results from therapy-induced damage to surrounding non-cancerous tissues, which leads to changes in the normal physiological functions of the various organs, including the small and large bowel. […] The initial stages of RBD involve damage to the epithelial tissue, a process that triggers an inflammatory response. For those patients who go on to develop RBD, this process will be followed by progressive ischaemia and fibrosis. […] Cells exposed to ionising radiation experience oxidative stress injuries. The damage is widespread; however, the principal subcellular target is the nuclear DNA. […] Both direct and indirect mechanisms inhibit DNA from fulfilling its function as a template for DNA transcription. The nuclear chromatin is directly targeted, causing DNA damage through the generation of inter and intra-strand cross-linkages, breaks, and mutations.

• #3 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  The imbalance of intestinal flora homeostasis disrupts the integrity of the intestinal epithelial barrier. […] Therefore, when ISCs are damaged, the proliferation of epithelial cells cannot supplement the death of epithelial cells in time, resulting in shortened villi, which subsequently reduces the intestinal surface area and intestinal absorption function. […] Researchers have found that the levels of claudin-2, claudin-3, claudin-4, claudin-10, JAM-1, and occludin are changed in the radiation group, which disturbs the epithelial barrier and increases intestinal permeability. […] The treatment of RIII is basically symptomatic and nutritional support treatment, such as anti-diarrhea, anti-vomiting, anti-inflammation, and surgical treatment, and an ideal means of prevention and treatment is lacking.

• #3 In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury | Scientific Reports

  https://www.nature.com/articles/srep15738

  The pathophysiological mechanism involved in side effects of radiation therapy and especially the role of the endothelium remains unclear. […] This work shows that PAI-1 plays a role in radiation-induced intestinal injury by an endothelium-dependent mechanism and demonstrates in vivo that the endothelium is directly involved in the progression of radiation-induced enteritis. […] The concept that the microvasculature plays a central role in the radiation toxicity of many tissues, including the intestine, is often described, but lacks robust demonstration. […] Irradiation leads to endothelial cell apoptosis, increased vascular permeability and acquisition of a pro-inflammatory and pro-coagulant phenotype. […] We previously showed that PAI-1 total knockout mice are protected against radiation enteritis, but there was no evidence that this was dependent on the PAI-1 endothelial pool.

• #3 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  The study suggests that abdominal radiation induces gut microbiota dysregulation and reduces the survival rate of irradiated mice in animal models. […] Existing research results show that the gut microbiota of patients with radiation enteritis is significantly translocated, the number of Actinobacteriota and Proteobacteria is significantly increased, and many conditional pathogenic bacteria, such as Enterococcus and Enterobacterales, are included. In summary, the study mentioned above shows that the gut microbiota of the patients with radiation enteritis changes significantly in terms of composition and diversity. […] The gut microbiota is closely related to radiation enteritis, but the current study is too shallow to elaborate its mechanism. More mechanistic studies are needed to provide evidence for alleviating radiation enteritis.

• #3 Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice – ADS

  https://ui.adsabs.harvard.edu/abs/2022JRadR..63..213L/abstract

  Patients receiving pelvic or abdominal radiotherapy may experience acute and/or chronic side effects due to gastrointestinal changes. […] In this study, we found that Liriodendrin can reduce the expression of Cer, Cer1P and S1P in the sphingolipid pathway, thereby reducing the histological damage to the intestinal tract of mice and inhibiting the apoptosis of intestinal tissue cells. […] Liriodendrin can reduce the levels of pro-inflammatory cytokines (IL-6 and TNF-), and it is suggested through flow cytometry that the proportion of neutrophils in the intestinal tissue can decrease due to the existence of Liriodendrin. […] The western blot evaluation revealed that Liriodendrin significantly inhibited the activation of Bcl-2/Bax/Caspase-3 and NF-B signaling pathways. […] The results show that Liriodendrin can inhibit intestinal inflammation and intestinal cell apoptosis through the sphingolipid pathway. […] Therefore, the aforementioned results demonstrated that Liriodendrin may be a promising drug for the treatment of radiation enteritis.

• #3 Diagnosis and management of chronic radiation enteritis – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-management-of-chronic-radiation-enteritis/print

  Injury to the intestines can occur following radiation therapy for cancer. It usually develops three or more months after radiation therapy. Chronic radiation enteritis is due to an obliterative arteritis that leads to intestinal ischemia, which can result in stricture, ulceration, fibrosis, and occasionally fistula formation. The physiologic consequences can include altered intestinal transit, reduced bile acid absorption, increased intestinal permeability, bacterial overgrowth, and lactose malabsorption. […] The pathogenesis, clinical manifestations, and risk factors for chronic radiation enteritis and other radiation-related gastrointestinal toxicities are discussed separately. […] The diagnosis of chronic radiation enteritis is suspected in patients with nausea, vomiting, abdominal pain, diarrhea, or lower gastrointestinal bleeding three or more months after completion of radiation therapy.

• #3 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  There is also evidence supporting a pivotal role for gut microbiota dysbiosis in the development of radiation-induced bowel injury. […] Radiation injury to the small and large bowel is due to damage to the lipid layer of the cell membrane, proteins, and cellular DNA. The effects are most marked in tissues containing cells with a high mitotic rate. […] The degree of intestinal injury is directly related to the total radiation dose, the fractionation, and the distribution of the dose in tissues peripheral to the target area. Early in the evolution of RT, large single radiation doses were noted to cause severe or even lethal adverse effects; the same cumulative dose given as small fractions over the course of several days or weeks was better tolerated. […] Excessive exposure of adjacent normal tissue to radiation also contributes to the development of radiation-induced enteropathy. Current techniques allow for a focused delivery of radiation energy to the target tissues with intracavitary radiation as well as external beam with supervoltage radiation, multiple portals, and the improved shielding of adjacent normal structures.

• #3 Clinical analysis of predisposing factors for radiation enteritis in patients with cervical cancer

  https://www.ejgo.net/articles/10.31083/j.ejgo4205143

  Objective: Radiation enteritis (RE) is one of the most common radiation-induced toxicities in patients with cervical cancer undergoing pelvic radiotherapy. […] Results: Incidences of acute RE (ARE) and chronic RE (CRE) were 65.2% and 13.1%, respectively. No prior surgery, radiation dose 56 Gy, hypertension, and hyperglycemia were found to be independent risk factors for ARE (95% confidence interval [CI], p 0.05). Hypertension, diabetes mellitus, and hyperglycemia were independent risk factors for CRE (95% CI, p 0.01). […] Conclusions: To reduce the occurrence of RE in patients with cervical cancer, comorbidities such as diabetes mellitus, hyperglycemia, and hypertension should be controlled, along with consideration of treatment-related factors such as the radiotherapy method and total radiation dose.

• #3 Radiation enteropathy – Wikipedia

  https://en.wikipedia.org/wiki/Radiation_enteropathy

  Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer. […] Early radiation enteropathy is very common during or immediately after the course of radiotherapy. This involves cell death, mucosal inflammation and epithelial barrier dysfunction. This injury is termed mucositis and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain. […] The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes intestinal epithelial mucosal atrophy, vascular sclerosis, and progressive fibrosis of the intestinal wall, among other changes in intestinal neuroendocrine and immune cells and in the gut microbiota. These changes may produce dysmotility, strictures, malabsorption and bleeding. Problems in the terminal ileum and rectum predominate.

• #3 Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats | BMC Complementary Medicine and Therapies | Full Text

  https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-025-04820-2

  Following the administration of CKI, expression of CB1 and Inflammatory factors was found to be decreased in rats compared with that in the radiotherapy model group. This effect was also observed following the administration of the CB1 agonist, while the administration of the CB1 inhibitor attenuated the effect of CKI. […] CKI treatment significantly reduced the pro-inflammatory factors and the expression of p38 MAPK signaling pathway-related proteins in the ileum of rats with RE, indicating that CKI can improve the inflammatory response and inhibit the activation of p38 MAPK signaling. […] Therefore, it can be hypothesised that CKI may improve radiation enteritis by mediating CB1 to inhibit the p38 MAPK pathway.

• #3 In vivo evidence for an endothelium-dependent mechanism in radiation-induced normal tissue injury | Scientific Reports

  https://www.nature.com/articles/srep15738

  Here, we show that irradiation very rapidly induces fibrin deposition. […] We showed that conditional endothelium-specific PAI-1 deletion limits radiation-induced macrophage infiltration (CD68+ cells) in the radiation acute phase. […] We demonstrate in this work that PAI-1 plays a role in the initiation of radiation-induced intestinal injury by an endothelium-dependent mechanism.

• #3 Network Pharmacology Analysis on the Mechanism of Xihuangwan in Treating Rectal Cancer and Radiation Enteritis – Lv – Current Pharmaceutical Design

  https://rjpbr.com/1381-6128/article/view/646020

  Recent studies have shown that XihuangWan (XHW) is a kind of Chinese medicine with significant anti-tumor and anti-inflammatory activities. However, its mechanism for preventing and treating radiation proctitis in rectal cancer patients during radiotherapy remains unclear. […] The active ingredients of XHW, mainly including Quercetin, Ellagic acid, and Stigmasterol, might act on common targets of rectal cancer and radiation enteritis, such as PTGS1, NR3C2, IL-6, EGFR, HIF-1A, CASP3, BCL2, ESR1, MYC, and PPARG, and regulate multiple signaling pathways like PI3K-Akt, TNF, and HIF-1 to inhibit tumor proliferation, tumor angiogenesis, inflammatory responses, and oxidative stress, thereby achieving prevention and treatment of radiation enteritis in rectal cancer patients during radiotherapy. It provided an important reference for further elucidating the anti-inflammation and anti-tumor mechanism and clinical application of XHW.

• #3 Research progress on the mechanism of radiation enteritis

  https://ouci.dntb.gov.ua/en/works/7BABnWg9/

  Radiation enteritis (Re) is one of the most common complications of radiation therapy for abdominal tumors. […] The underlying mechanisms of Re are complex and have not yet been elucidated. The purpose of this review is to provide an overview of the pathogenesis of Re. We reviewed the role of intestinal epithelial cells, intestinal stem cells (ISCs), vascular endothelial cells (ECs), intestinal microflora, and other mediators of Re, noting that a better understanding of the pathogenesis of Re may lead to better treatment modalities. […] Severe acute and chronic radiation enteritis result from the damage to the crypt-based intestinal stem cells and their derivatives, which include the Paneth cells. Paneth cells regulate the proliferation and differentiation of the intestinal stem cells. The effect of ionizing radiation on the intestinal stem cells and its derivatives, and the knowledge can be used to develop effective treatment of radiation enteritis is discussed.

• #4 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  Radiation damages vascular endothelial cells in various ways, resulting in endothelial cell swelling, increased permeability, inflammatory cell adhesion and migration, and microthrombosis in microvessels. […] The senescence of endothelial cells results in a senescence-related secretory phenotype in which endothelial cells secrete cytokines, proteins, and other factors that cause dysfunction in neighboring cells or contribute to a chronic inflammatory state. […] The intestinal immune system plays a pivotal role in the maintenance of intestinal homeostasis, and its imbalance is closely related to intestinal diseases. […] In RIII, the levels of immune cells and immune cytokines changed, suggesting an important role of immune imbalance in RIII. […] There is evidence that the pathophysiology of RIII is correlated with intestinal microbiota dysregulation.

• #4 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  The study suggests that abdominal radiation induces gut microbiota dysregulation and reduces the survival rate of irradiated mice in animal models. […] Existing research results show that the gut microbiota of patients with radiation enteritis is significantly translocated, the number of Actinobacteriota and Proteobacteria is significantly increased, and many conditional pathogenic bacteria, such as Enterococcus and Enterobacterales, are included. In summary, the study mentioned above shows that the gut microbiota of the patients with radiation enteritis changes significantly in terms of composition and diversity. […] The gut microbiota is closely related to radiation enteritis, but the current study is too shallow to elaborate its mechanism. More mechanistic studies are needed to provide evidence for alleviating radiation enteritis.

• #4 Radiation colitis – wikidoc

  https://www.wikidoc.org/index.php/Radiation_colitis

  Radiation colitis occurs following radiation therapy for abdominal and pelvic malignancies. […] It is more common with radiation doses higher than 45Gy. […] The main site of damage is DNA. The pathogenesis involves direct ionizing damage to the DNA resulting in inhibition of mitosis. Radiation may also affect RNA, proteins, and cell membranes. Oxidative injury to the DNA may also contribute to the development of radiation colitis. […] Injury may occur a few hours to days, up to three months after irradiation in acute radiation colitis. It affects rapidly dividing cells of the epithelium and mucosa crypts. This leads to cell death, recruitment and activation of polymorphonuclear (PMN) inflammatory cells, mucosal edema and damage to small blood vessels. The effect of this damage to the mucosa is fluid, electrolyte and nutrient loss. Radiation also reduces bowel motility. Acute radiation colitis is usually transient and self limiting, with regeneration of the epithelium.

• #4 Diagnosis and management of chronic radiation enteritis – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-management-of-chronic-radiation-enteritis/print

  Injury to the intestines can occur following radiation therapy for cancer. It usually develops three or more months after radiation therapy. Chronic radiation enteritis is due to an obliterative arteritis that leads to intestinal ischemia, which can result in stricture, ulceration, fibrosis, and occasionally fistula formation. The physiologic consequences can include altered intestinal transit, reduced bile acid absorption, increased intestinal permeability, bacterial overgrowth, and lactose malabsorption. […] The pathogenesis, clinical manifestations, and risk factors for chronic radiation enteritis and other radiation-related gastrointestinal toxicities are discussed separately. […] The diagnosis of chronic radiation enteritis is suspected in patients with nausea, vomiting, abdominal pain, diarrhea, or lower gastrointestinal bleeding three or more months after completion of radiation therapy.

• #4 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  There is also evidence supporting a pivotal role for gut microbiota dysbiosis in the development of radiation-induced bowel injury. […] Radiation injury to the small and large bowel is due to damage to the lipid layer of the cell membrane, proteins, and cellular DNA. The effects are most marked in tissues containing cells with a high mitotic rate. […] The degree of intestinal injury is directly related to the total radiation dose, the fractionation, and the distribution of the dose in tissues peripheral to the target area. Early in the evolution of RT, large single radiation doses were noted to cause severe or even lethal adverse effects; the same cumulative dose given as small fractions over the course of several days or weeks was better tolerated. […] Excessive exposure of adjacent normal tissue to radiation also contributes to the development of radiation-induced enteropathy. Current techniques allow for a focused delivery of radiation energy to the target tissues with intracavitary radiation as well as external beam with supervoltage radiation, multiple portals, and the improved shielding of adjacent normal structures.

• #4 Radiation Enteritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK526032/

  Radiation enteritis is damage to the small and/or large intestines secondary to radiation. Different terms like radiation colitis, radiation enteropathy, radiation mucositis, and pelvic radiation disease have been used to describe this phenomenon. Radiation proctitis is a different term that is used to describe the involvement of the rectum and sigmoid colon. Radiotherapy is used as a treatment for many cancers. Radiation enteritis can be acute or chronic. The chronic form usually develops between 3 months to 30 years after treatment. […] Radiation enteritis is an unavoidable side effect of radiotherapy, although its development is highly variable, depending on the duration, dosage, and gut sensitivity to radiation. […] The repetitive injuries caused to the intestinal mucosa by ionizing radiation, as well as its complex mechanism of healing, are proposed to cause radiation enteritis. Exposure of normal tissues to radiation leads to the production of reactive ions that combine with intracellular water molecules to form radicals like hydroxyl and other free radicals. These radicals are deemed responsible for causing breaks in DNA and causing cell death. Secondary to radiation exposure, activation of genes that are responsible for the translation of transforming growth factor (TGF-beta) takes place. This activation stimulates collagen and fibronectin genes promoting fibrosis. Tissues with rapid proliferation are sensitive to radiation, and thus, cell membrane disruption is also responsible for the cell death observed. The epithelial cells of the small intestine are more radiosensitive as compared to the colon and rectum. Studies show that the presence of Bcl2 in the rectum is the reason for this discrimination. The most characteristic pathologic changes observed are fibrosis and obliterative endarteritis in the intestinal epithelium.

• #4 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  Histopathologic findings in acute radiation-related intestinal damage include the following characteristics: […] In addition, mitotic arrest, karyorrhexis, and lysis of the crypt and deep epithelial cells are observed. If the submucosal damage is not prominent, the epithelial cells regenerate and the changes regress. Conversely, severe submucosal changes lead to progression of mucosal injury, ulcerations, and erosion of the villi. The histologic findings in the acute phase correlate poorly with clinical symptoms, but amounts of malabsorption vary because of the mucosal damage. […] Histologically, obliterative endarteritis of the small vessels in the intestinal wall characterizes chronic radiation injury to the intestine. Associated lymphoid atrophy, lymphatic dilation, and fibrosis of the submucosal tissue are observed. The progressive vascular sclerosis leads to chronic ischemia of the overlying tissue, ultimately resulting in mucosal atrophy. Scar tissue replaces the submucosal tissue, resulting in further decrease in vascularity and contracture of the intestinal wall. Chronic mucosal ulceration may result in fistula formation and hemorrhage.

• #4 Compound kushen injection improves radiation enteritis via cannabinoid receptor 1 in rats | BMC Complementary Medicine and Therapies | Full Text

  https://bmccomplementmedtherapies.biomedcentral.com/articles/10.1186/s12906-025-04820-2

  Following the administration of CKI, expression of CB1 and Inflammatory factors was found to be decreased in rats compared with that in the radiotherapy model group. This effect was also observed following the administration of the CB1 agonist, while the administration of the CB1 inhibitor attenuated the effect of CKI. […] CKI treatment significantly reduced the pro-inflammatory factors and the expression of p38 MAPK signaling pathway-related proteins in the ileum of rats with RE, indicating that CKI can improve the inflammatory response and inhibit the activation of p38 MAPK signaling. […] Therefore, it can be hypothesised that CKI may improve radiation enteritis by mediating CB1 to inhibit the p38 MAPK pathway.

• #4 Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice. | EBSCOhost

  https://search.ebscohost.com/login.aspx?direct=true&profile=ehost&scope=site&authtype=crawler&jrnl=04493060&AN=156007047&h=MclqldONEiD4AwNJwgVZhfl5EHuPYOkMhBV8J1AXCq3mjsnwkkeuC%2FK38GPorMleTpyYtniqGrMQAHAS3o1Crg%3D%3D&crl=f

  Study on the protective effect and mechanism of Liriodendrin on radiation enteritis in mice. […] In this study, we found that Liriodendrin can reduce the expression of Cer, Cer1P and S1P in the sphingolipid pathway, thereby reducing the histological damage to the intestinal tract of mice and inhibiting the apoptosis of intestinal tissue cells. […] The results show that Liriodendrin can inhibit intestinal inflammation and intestinal cell apoptosis through the sphingolipid pathway. Therefore, the aforementioned results demonstrated that Liriodendrin may be a promising drug for the treatment of radiation enteritis.

• #4 Family

  https://patents.google.com/patent/ES2538478T3/en

  Rifaximina jest szczególnie korzystna, ponieważ nie jest wchłaniana i nie powoduje zakłócenia normalnej flory (szczególnie jelita cienkiego), co predysponuje pacjentów do nadmiernego wzrostu bakterii patogennych, a leczenie rifaksyminą może leczyć i zapobiegać temu nadmiernemu wzrostowi bakterii. […] Mechanizm biegunki wywołanej promieniowaniem obejmuje ostre uszkodzenie mechaniczne komórek krypt nabłonka przewodu pokarmowego. […] Uszkodzenie tego typu prowadzi do śmierci komórki (czy to przez mechanizm martwiczy, czy apoptyczny), zapalenie i owrzodzenie błony śluzowej jelit, które następnie jest narażone na drażniące sole żółciowe i staje się podatne na infekcje oportunistyczne. […] W przypadku ciężkich przypadków może wystąpić ostra niedrożność jelit, przetoki lub perforacja jelit.

• #4 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  The intestinal mucosal epithelial cells, together with the basement membrane, constitute the intestinal epithelial mechanical barrier. […] However, the epithelium of the small intestine renews very quickly and is extremely sensitive to radiation, which disrupts its integrity. […] Radiation can cause DNA damage to intestinal epithelial cells via direct or indirect means, leading to cell death and tight junction damage, which subsequently disrupt the integrity of the intestinal mechanical barrier. […] After exposure to ionizing radiation, the main death mode of intestinal epithelial cells is apoptosis. […] Studies have shown that p53 plays an important role in radiation response after intestinal injury. […] In addition to apoptosis, recent studies have shown that autophagy, pyroptosis, and ferroptosis are also involved in radiation-induced intestinal epithelial injury.

• #5 Diagnosis and management of chronic radiation enteritis – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-management-of-chronic-radiation-enteritis/print

  Injury to the intestines can occur following radiation therapy for cancer. It usually develops three or more months after radiation therapy. Chronic radiation enteritis is due to an obliterative arteritis that leads to intestinal ischemia, which can result in stricture, ulceration, fibrosis, and occasionally fistula formation. The physiologic consequences can include altered intestinal transit, reduced bile acid absorption, increased intestinal permeability, bacterial overgrowth, and lactose malabsorption. […] The pathogenesis, clinical manifestations, and risk factors for chronic radiation enteritis and other radiation-related gastrointestinal toxicities are discussed separately. […] The diagnosis of chronic radiation enteritis is suspected in patients with nausea, vomiting, abdominal pain, diarrhea, or lower gastrointestinal bleeding three or more months after completion of radiation therapy.

• #5 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  There is also evidence supporting a pivotal role for gut microbiota dysbiosis in the development of radiation-induced bowel injury. […] Radiation injury to the small and large bowel is due to damage to the lipid layer of the cell membrane, proteins, and cellular DNA. The effects are most marked in tissues containing cells with a high mitotic rate. […] The degree of intestinal injury is directly related to the total radiation dose, the fractionation, and the distribution of the dose in tissues peripheral to the target area. Early in the evolution of RT, large single radiation doses were noted to cause severe or even lethal adverse effects; the same cumulative dose given as small fractions over the course of several days or weeks was better tolerated. […] Excessive exposure of adjacent normal tissue to radiation also contributes to the development of radiation-induced enteropathy. Current techniques allow for a focused delivery of radiation energy to the target tissues with intracavitary radiation as well as external beam with supervoltage radiation, multiple portals, and the improved shielding of adjacent normal structures.

• #5 The impact of pelvic radiotherapy on the gut microbiome and its role in radiation-induced diarrhoea: a systematic review | Radiation Oncology | Full Text

  https://ro-journal.biomedcentral.com/articles/10.1186/s13014-021-01899-y

  As the included studies reported, the gut microbiota is disturbed during and after pelvic radiotherapy. 16S RNA technology revealed that the diversity of intestinal flora communities at different time points before, during, and after pelvic radiotherapy was significantly decreased. In addition, the diversity of intestinal flora was decreased more significantly in patients who experienced diarrhoea after radiotherapy. These studies provide vital evidence for a link between the alterations in microbiota caused by radiotherapy and postradiotherapy diarrhoea. However, they do not shed light on the mechanistic relationship between microbiota and bowel injury in those who developed postirradiation diarrhoea. […] In the literature included in this study, five studies reported significant differences in the distribution of bacteria before radiation therapy among patients with radiation-induced diarrhoea, patients without diarrhoea after radiotherapy, and healthy volunteers. On the one hand, the composition of intestinal bacteria before radiotherapy in patients determines whether diarrhoea will occur after radiotherapy, and the microenvironment created by intestinal bacteria and their products is an important factor affecting the occurrence of diarrhoea after radiotherapy. On the other hand, intestinal bacteria change significantly during and after the end of radiotherapy, and changes in these specific species are also responsible for intestinal epithelial damage and diarrhoea.

• #5 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  Histopathologic findings in acute radiation-related intestinal damage include the following characteristics: […] In addition, mitotic arrest, karyorrhexis, and lysis of the crypt and deep epithelial cells are observed. If the submucosal damage is not prominent, the epithelial cells regenerate and the changes regress. Conversely, severe submucosal changes lead to progression of mucosal injury, ulcerations, and erosion of the villi. The histologic findings in the acute phase correlate poorly with clinical symptoms, but amounts of malabsorption vary because of the mucosal damage. […] Histologically, obliterative endarteritis of the small vessels in the intestinal wall characterizes chronic radiation injury to the intestine. Associated lymphoid atrophy, lymphatic dilation, and fibrosis of the submucosal tissue are observed. The progressive vascular sclerosis leads to chronic ischemia of the overlying tissue, ultimately resulting in mucosal atrophy. Scar tissue replaces the submucosal tissue, resulting in further decrease in vascularity and contracture of the intestinal wall. Chronic mucosal ulceration may result in fistula formation and hemorrhage.

• #5 Family

  https://patents.google.com/patent/ES2538478T3/en

  Rifaximina może być podawana, na przykład, dwa razy dziennie, trzy razy dziennie lub cztery razy dziennie. […] Rifaximina może być podawana, na przykład, w postaci tabletki, proszku, płynnej lub w kapsułkach. […] Rifaximina może być podawana przed, w trakcie i/lub po terapii promieniowaniem. […] Rifaximina jest stosowana w leczeniu enteritis wywołanej promieniowaniem, co jest szczególnie korzystne, ponieważ nie powoduje zakłócenia normalnej flory jelitowej.

• #5 Radiation enteropathy – Wikipedia

  https://en.wikipedia.org/wiki/Radiation_enteropathy

  Radiation enteropathy is a syndrome that may develop following abdominal or pelvic radiation therapy for cancer. […] Early radiation enteropathy is very common during or immediately after the course of radiotherapy. This involves cell death, mucosal inflammation and epithelial barrier dysfunction. This injury is termed mucositis and results in symptoms of nausea, vomiting, fatigue, diarrhea and abdominal pain. […] The delayed effects, found 3 months or more after radiation therapy, produce pathology which includes intestinal epithelial mucosal atrophy, vascular sclerosis, and progressive fibrosis of the intestinal wall, among other changes in intestinal neuroendocrine and immune cells and in the gut microbiota. These changes may produce dysmotility, strictures, malabsorption and bleeding. Problems in the terminal ileum and rectum predominate.

• #6 Diagnosis and management of chronic radiation enteritis – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-management-of-chronic-radiation-enteritis/print

  Injury to the intestines can occur following radiation therapy for cancer. It usually develops three or more months after radiation therapy. Chronic radiation enteritis is due to an obliterative arteritis that leads to intestinal ischemia, which can result in stricture, ulceration, fibrosis, and occasionally fistula formation. The physiologic consequences can include altered intestinal transit, reduced bile acid absorption, increased intestinal permeability, bacterial overgrowth, and lactose malabsorption. […] The pathogenesis, clinical manifestations, and risk factors for chronic radiation enteritis and other radiation-related gastrointestinal toxicities are discussed separately. […] The diagnosis of chronic radiation enteritis is suspected in patients with nausea, vomiting, abdominal pain, diarrhea, or lower gastrointestinal bleeding three or more months after completion of radiation therapy.

• #6 Radiation enteritis: What it is, symptoms, causes, and more

  https://www.medicalnewstoday.com/articles/radiation-enteritis

  Radiation enteritis is more likely to occur in people who have received high doses of radiation for cancer treatment to large areas of their intestines and abdomen. Receiving chemotherapy alongside radiation therapy can increase a persons risk of developing this condition. […] Treatment focuses on reducing symptoms until the inflammation resolves. In severe cases, people may have to undergo surgery to remove parts of their intestines.

• #6 Radiation colitis – wikidoc

  https://www.wikidoc.org/index.php/Radiation_colitis

  Radiation colitis occurs following radiation therapy for abdominal and pelvic malignancies. […] It is more common with radiation doses higher than 45Gy. […] The main site of damage is DNA. The pathogenesis involves direct ionizing damage to the DNA resulting in inhibition of mitosis. Radiation may also affect RNA, proteins, and cell membranes. Oxidative injury to the DNA may also contribute to the development of radiation colitis. […] Injury may occur a few hours to days, up to three months after irradiation in acute radiation colitis. It affects rapidly dividing cells of the epithelium and mucosa crypts. This leads to cell death, recruitment and activation of polymorphonuclear (PMN) inflammatory cells, mucosal edema and damage to small blood vessels. The effect of this damage to the mucosa is fluid, electrolyte and nutrient loss. Radiation also reduces bowel motility. Acute radiation colitis is usually transient and self limiting, with regeneration of the epithelium.

• #6 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  Histopathologic findings in acute radiation-related intestinal damage include the following characteristics: […] In addition, mitotic arrest, karyorrhexis, and lysis of the crypt and deep epithelial cells are observed. If the submucosal damage is not prominent, the epithelial cells regenerate and the changes regress. Conversely, severe submucosal changes lead to progression of mucosal injury, ulcerations, and erosion of the villi. The histologic findings in the acute phase correlate poorly with clinical symptoms, but amounts of malabsorption vary because of the mucosal damage. […] Histologically, obliterative endarteritis of the small vessels in the intestinal wall characterizes chronic radiation injury to the intestine. Associated lymphoid atrophy, lymphatic dilation, and fibrosis of the submucosal tissue are observed. The progressive vascular sclerosis leads to chronic ischemia of the overlying tissue, ultimately resulting in mucosal atrophy. Scar tissue replaces the submucosal tissue, resulting in further decrease in vascularity and contracture of the intestinal wall. Chronic mucosal ulceration may result in fistula formation and hemorrhage.

• #6

  https://journals.lww.com/ajg/fulltext/2014/10002/improvement_of_chronic_diarrhea_associated_with.1347.aspx

  Radiation enteritis is a well-described complication of pelvic or abdominal radiation therapy. […] The most common mechanism to explain diarrhea in chronic radiation enteritis is bile acid malabsorption. Excess bile salts in the colon stimulate water secretion, leading to increased motility and diarrhea. […] Cholestyramine irreversibly binds bile salts, thus acting as a surrogate ileum and preventing concomitant electrolyte and water secretion into the colon.

• #7 Radiation colitis – wikidoc

  https://www.wikidoc.org/index.php/Radiation_colitis

  Radiation colitis occurs following radiation therapy for abdominal and pelvic malignancies. […] It is more common with radiation doses higher than 45Gy. […] The main site of damage is DNA. The pathogenesis involves direct ionizing damage to the DNA resulting in inhibition of mitosis. Radiation may also affect RNA, proteins, and cell membranes. Oxidative injury to the DNA may also contribute to the development of radiation colitis. […] Injury may occur a few hours to days, up to three months after irradiation in acute radiation colitis. It affects rapidly dividing cells of the epithelium and mucosa crypts. This leads to cell death, recruitment and activation of polymorphonuclear (PMN) inflammatory cells, mucosal edema and damage to small blood vessels. The effect of this damage to the mucosa is fluid, electrolyte and nutrient loss. Radiation also reduces bowel motility. Acute radiation colitis is usually transient and self limiting, with regeneration of the epithelium.

• #7 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  Histopathologic findings in acute radiation-related intestinal damage include the following characteristics: […] In addition, mitotic arrest, karyorrhexis, and lysis of the crypt and deep epithelial cells are observed. If the submucosal damage is not prominent, the epithelial cells regenerate and the changes regress. Conversely, severe submucosal changes lead to progression of mucosal injury, ulcerations, and erosion of the villi. The histologic findings in the acute phase correlate poorly with clinical symptoms, but amounts of malabsorption vary because of the mucosal damage. […] Histologically, obliterative endarteritis of the small vessels in the intestinal wall characterizes chronic radiation injury to the intestine. Associated lymphoid atrophy, lymphatic dilation, and fibrosis of the submucosal tissue are observed. The progressive vascular sclerosis leads to chronic ischemia of the overlying tissue, ultimately resulting in mucosal atrophy. Scar tissue replaces the submucosal tissue, resulting in further decrease in vascularity and contracture of the intestinal wall. Chronic mucosal ulceration may result in fistula formation and hemorrhage.

• #7 Role of triamcinolone in radiation enteritis management

  https://www.wjgnet.com/1007-9327/full/v20/i15/4341.htm

  Typically, 8 to 12 mo after radiotherapy, obliterative endarteritis occurs as a vascular occlusion, followed by tissue growth factor (TGF)-induced tissue ischemia, necrosis and fibrosis. Additionally, angiogenesis and chronic inflammation are seen after vascular endothelial growth factor (VEGF) secretion. […] In contrast, glucocorticoids are used for a vast number of inflammatory diseases. Long term use cause side effects. These drugs inhibit MMP2 secretion and prevent leucocytes infiltrations and TNF-induced inflammatory and angiogenic steps. Steroids are effective agents for preventing leucocyte infiltration, mucosal inflammation and edema. […] A steroid drug would be preferable because it might prevent the tissue reactions to radiation at some molecular steps. […] In our study, TA was found to be effective for preventing and treating radiation-induced acute GIS and GUS side effects.

• #7 Diagnosis and management of chronic radiation enteritis – UpToDate

  https://www.uptodate.com/contents/diagnosis-and-management-of-chronic-radiation-enteritis/print

  Injury to the intestines can occur following radiation therapy for cancer. It usually develops three or more months after radiation therapy. Chronic radiation enteritis is due to an obliterative arteritis that leads to intestinal ischemia, which can result in stricture, ulceration, fibrosis, and occasionally fistula formation. The physiologic consequences can include altered intestinal transit, reduced bile acid absorption, increased intestinal permeability, bacterial overgrowth, and lactose malabsorption. […] The pathogenesis, clinical manifestations, and risk factors for chronic radiation enteritis and other radiation-related gastrointestinal toxicities are discussed separately. […] The diagnosis of chronic radiation enteritis is suspected in patients with nausea, vomiting, abdominal pain, diarrhea, or lower gastrointestinal bleeding three or more months after completion of radiation therapy.

• #8 Radiation colitis – wikidoc

  https://www.wikidoc.org/index.php/Radiation_colitis

  Radiation colitis occurs following radiation therapy for abdominal and pelvic malignancies. […] It is more common with radiation doses higher than 45Gy. […] The main site of damage is DNA. The pathogenesis involves direct ionizing damage to the DNA resulting in inhibition of mitosis. Radiation may also affect RNA, proteins, and cell membranes. Oxidative injury to the DNA may also contribute to the development of radiation colitis. […] Injury may occur a few hours to days, up to three months after irradiation in acute radiation colitis. It affects rapidly dividing cells of the epithelium and mucosa crypts. This leads to cell death, recruitment and activation of polymorphonuclear (PMN) inflammatory cells, mucosal edema and damage to small blood vessels. The effect of this damage to the mucosa is fluid, electrolyte and nutrient loss. Radiation also reduces bowel motility. Acute radiation colitis is usually transient and self limiting, with regeneration of the epithelium.

• #8 Radiation Enteritis and Proctitis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/197483-overview

  Histopathologic findings in acute radiation-related intestinal damage include the following characteristics: […] In addition, mitotic arrest, karyorrhexis, and lysis of the crypt and deep epithelial cells are observed. If the submucosal damage is not prominent, the epithelial cells regenerate and the changes regress. Conversely, severe submucosal changes lead to progression of mucosal injury, ulcerations, and erosion of the villi. The histologic findings in the acute phase correlate poorly with clinical symptoms, but amounts of malabsorption vary because of the mucosal damage. […] Histologically, obliterative endarteritis of the small vessels in the intestinal wall characterizes chronic radiation injury to the intestine. Associated lymphoid atrophy, lymphatic dilation, and fibrosis of the submucosal tissue are observed. The progressive vascular sclerosis leads to chronic ischemia of the overlying tissue, ultimately resulting in mucosal atrophy. Scar tissue replaces the submucosal tissue, resulting in further decrease in vascularity and contracture of the intestinal wall. Chronic mucosal ulceration may result in fistula formation and hemorrhage.

• #8 Effect of pentoxifylline and tocopherol on radiation proctitis/enteritis

  https://inis.iaea.org/search/search.aspx?orig_q=RN:37038869

  Chronic radiation proctitis/enteritis is a relevant complication of pelvic irradiation, which is still mainly treated by supportive measures only. There is some evidence that the combined treatment with pentoxifylline and tocopherol might alter the pathogenesis of radiation-induced fibrosis. […] The combination treatment with pentoxifylline and tocopherol seems to have a benefit in patients with grade I-II radiation-induced proctitis/enteritis. […] From the observations made in this study it is assumed the treatment should be given for 6-12 months at least.

• #8 Radiation Enteritis – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK526032/

  Radiation enteritis is damage to the small and/or large intestines secondary to radiation. Different terms like radiation colitis, radiation enteropathy, radiation mucositis, and pelvic radiation disease have been used to describe this phenomenon. Radiation proctitis is a different term that is used to describe the involvement of the rectum and sigmoid colon. Radiotherapy is used as a treatment for many cancers. Radiation enteritis can be acute or chronic. The chronic form usually develops between 3 months to 30 years after treatment. […] Radiation enteritis is an unavoidable side effect of radiotherapy, although its development is highly variable, depending on the duration, dosage, and gut sensitivity to radiation. […] The repetitive injuries caused to the intestinal mucosa by ionizing radiation, as well as its complex mechanism of healing, are proposed to cause radiation enteritis. Exposure of normal tissues to radiation leads to the production of reactive ions that combine with intracellular water molecules to form radicals like hydroxyl and other free radicals. These radicals are deemed responsible for causing breaks in DNA and causing cell death. Secondary to radiation exposure, activation of genes that are responsible for the translation of transforming growth factor (TGF-beta) takes place. This activation stimulates collagen and fibronectin genes promoting fibrosis. Tissues with rapid proliferation are sensitive to radiation, and thus, cell membrane disruption is also responsible for the cell death observed. The epithelial cells of the small intestine are more radiosensitive as compared to the colon and rectum. Studies show that the presence of Bcl2 in the rectum is the reason for this discrimination. The most characteristic pathologic changes observed are fibrosis and obliterative endarteritis in the intestinal epithelium.

• #9 (PDF) REVIEW ARTICLE ON RADIATION-INDUCED PROCTITIS & ENTERITIS

  https://www.academia.edu/84046040/REVIEW_ARTICLE_ON_RADIATION_INDUCED_PROCTITIS_and_ENTERITIS

  The hyperstimulation of transforming growth factor 1 (TGF-1) leads to increased fibrosis and, ultimately, organ failure. […] Radiation enteritis and other radiation-induced, long-term complications are characterized by excessive stimulation of TGF-1. […] The manifestations of late radiation enteropathy are primarily due to changes in compartments other than the mucosa, such as intestinal wall fibrosis and obliterating vascular sclerosis. […] The present paper summarizes clinical, pathophysiologic, and radiobiologic aspects pertinent to the development of chronic intestinal radiation injury.

• #10 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  Radiation enteritis is a kind of intestinal radiation injury in patients with pelvic and retroperitoneal malignancies after radiotherapy, and its occurrence and development process are very complicated. At present, studies have confirmed that intestinal microecological imbalance is an important factor in the formation of this disease. Abdominal radiation causes changes in the composition of the flora and a decrease in its diversity, which is mainly manifested by a decrease in beneficial bacterial species such as Lactobacilli and Bifidobacteria. Intestinal dysbacteriosis aggravates radiation enteritis, weakens the function of the intestinal epithelial barrier, and promotes the expression of inflammatory factors, thereby aggravating the occurrence of enteritis. […] Radiation enteritis is caused by the dynamic interaction of intestinal microbiome changes, epithelial cell injury and repair, endothelial cell injury and remodeling, fibroplasia, and enteric nervous system changes. The basic pathological changes include two aspects: intestinal mucosal injury caused by radiation and vascular connective tissue injury caused by radiation vascular endothelial cells.

• #11 Research progress and treatment of radiation enteritis and gut microbiota

  https://www.e-roj.org/journal/view.php?doi=10.3857/roj.2023.00346

  The study suggests that abdominal radiation induces gut microbiota dysregulation and reduces the survival rate of irradiated mice in animal models. […] Existing research results show that the gut microbiota of patients with radiation enteritis is significantly translocated, the number of Actinobacteriota and Proteobacteria is significantly increased, and many conditional pathogenic bacteria, such as Enterococcus and Enterobacterales, are included. In summary, the study mentioned above shows that the gut microbiota of the patients with radiation enteritis changes significantly in terms of composition and diversity. […] The gut microbiota is closely related to radiation enteritis, but the current study is too shallow to elaborate its mechanism. More mechanistic studies are needed to provide evidence for alleviating radiation enteritis.

• #12

  https://journals.lww.com/ajg/fulltext/2014/10002/improvement_of_chronic_diarrhea_associated_with.1347.aspx

  Radiation enteritis is a well-described complication of pelvic or abdominal radiation therapy. […] The most common mechanism to explain diarrhea in chronic radiation enteritis is bile acid malabsorption. Excess bile salts in the colon stimulate water secretion, leading to increased motility and diarrhea. […] Cholestyramine irreversibly binds bile salts, thus acting as a surrogate ileum and preventing concomitant electrolyte and water secretion into the colon.

• #13 Radiation-Induced Enteritis: Incidence, Mechanisms, and Management

  https://www.cancernetwork.com/view/radiation-induced-enteritis-incidence-mechanisms-and-management

  Radiation-induced diarrhea can be severe and life threatening. It is obvious that by reducing the chemoradiation-induced bowel symptoms, the patients quality of life during (and following) therapy can be enhanced. Additionally, minimizing the severity of radiation-induced enteritis may increase the probability of completing the planned treatment without interruption and improve the outcome. It is also expected that effective management/prevention of severe diarrhea would avoid hospitalization for complications such as dehydration, fluid and electrolyte imbalance, or nutritional decline. […] The pathophysiology of radiation enteritis is not well understood. Radiation-induced mucosal damage results in decreased absorption of water and electrolytes, causing diarrhea. Another possible mechanism is decreased bile acid absorption in the ileum (due to mucosal damage). When passing through the bowel, the excess bile acid irritates and damages the protective mucosal cap of the intestine. This results in transudation of fluid and electrolytes into the lumen and causes diarrhea. […] Conventional antidiarrheal agents fail to prevent the onset of grade 3/4 diarrhea.

• #14 Radiation-Induced Intestinal Injury: Injury Mechanism and Potential Treatment Strategies

  https://www.mdpi.com/2305-6304/11/12/1011

  Radiation damages vascular endothelial cells in various ways, resulting in endothelial cell swelling, increased permeability, inflammatory cell adhesion and migration, and microthrombosis in microvessels. […] The senescence of endothelial cells results in a senescence-related secretory phenotype in which endothelial cells secrete cytokines, proteins, and other factors that cause dysfunction in neighboring cells or contribute to a chronic inflammatory state. […] The intestinal immune system plays a pivotal role in the maintenance of intestinal homeostasis, and its imbalance is closely related to intestinal diseases. […] In RIII, the levels of immune cells and immune cytokines changed, suggesting an important role of immune imbalance in RIII. […] There is evidence that the pathophysiology of RIII is correlated with intestinal microbiota dysregulation.

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