Research progress on the mechanism of radiation enteritis

Fan, Jinjia; Lin, Baihan; Fan, Minguang; Niu, Tintin; Gao, Feng; Tan, Bangxian; Du, Xiaobo

doi:10.3389/fonc.2022.888962

Cited by 15 publications

(8 citation statements)

References 71 publications

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“…Among these three time points, the apoptosis of human small intestinal mucosal epithelial cells was the most evident and sDR5-Fc was the most effective in blocking apoptosis at 48 h after radiation. Radiation damages the intestinal mucosa and causes acute radiation enteritis ( Singh and Seed, 2019 ; Fan et al, 2022 ). The intestinal mucosal barrier plays a crucial role in protecting against the invasion of foreign antigens, maintaining the stability of the internal environment, as well as the normal activities of the body ( Turner, 2009 ).…”

Section: Resultsmentioning

confidence: 99%

Blocking TRAIL-DR5 signaling pathway with soluble death receptor 5 fusion protein mitigates radiation-induced injury

et al. 2023

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The increasing application of nuclear technology, the high fatality of acute radiation syndrome (ARS) and its complex mechanism make ARS a global difficulty that requires urgent attention. Here we reported that the death receptor 5 (DR5), as well as its ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), were both significantly upregulated after irradiation in mice with 6 Gy γ-ray single radiation. And by intravenously administrated with soluble DR5 fusion protein (sDR5-Fc), the competitive antagonist of DR5, the excessive apoptosis in the radiation-sensitive tissues such as spleen and thymus were significantly inhibited and the radiation-induced damage of spleen and thymus were mitigated, while the expression of apoptosis-inhibiting proteins such as Bcl-2 was also significantly upregulated. The biochemical indicators such as serum ALP, AST, ALT, TBIL, K, and Cl levels that affected by radiation, were improved by sDR5-Fc administration. sDR5-Fc can also regulate the number of immune cells and reduce blood cell death. For in vitro studies, it had been found that sDR5-Fc effectively inhibited apoptosis of human small intestinal mucosal epithelial cells and IEC-6 cells using flow cytometry. Finally, survival studies showed that mice administrated with sDR5-Fc after 9 Gy γ-ray single whole body radiation effectively increased the 30-day survival and was in a significant dose-dependent manner. Overall, the findings revealed that DR5/TRAIL-mediated apoptosis pathway had played important roles in the injury of ARS mice, and DR5 probably be a potential target for ARS therapeutics. And the DR5 apoptosis antagonist, sDR5 fusion protein, probably is a promising anti-ARS drug candidate which deserves further investigation.

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Section: Resultsmentioning

confidence: 99%

Blocking TRAIL-DR5 signaling pathway with soluble death receptor 5 fusion protein mitigates radiation-induced injury

et al. 2023

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“…In terms of the mechanism of radiation enteritis, the existing research shows that, on the one hand, radiation can directly affect the DNA and membrane proteins of intestinal epithelium during radiotherapy, causing the intestinal epithelium to undergo cleavage and apoptosis, and the integrity of intestinal mechanical barrier is destroyed [4,27]. On the other hand, due to the high sensitivity and poor tolerance of intestinal stem cells to radiation therapy, the proliferation and differentiation of intestinal stem cells into intestinal epithelial cells were blocked by radiation therapy, the number of intestinal epithelial cells decreased sharply, and the damage of intestinal mechanical barrier was further aggravated [28].…”

Section: Discussionmentioning

confidence: 99%

“…It is characterized by apparent pathological damage of intestinal mucosa and death of intestinal crypt epithelial cells, which causes in ammation and brosis of the intestine, causing loss of appetite, nausea, abdominal pain, bloating, and diarrhea. There is much research on the treatment of radiation enteropathy, but much of them are still focused on symptomatic therapy, and the results are not good [3][4][5][6][7]. Overall, radioactive enteritis still lacks effective therapeutic targets.…”

Section: Introductionmentioning

confidence: 99%

Single Cell Atlas of Murine Crypt with Acute Radiation Enteritis

Chang,

Li,

Guo

et al. 2023

Preprint

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Although intestinal stem cells (ISC) from the basement of the intestinal crypt play an essential role in intestinal mucosal repair and epithelial regeneration, and stem cell transplantation is effective in treating rats and dogs with radioactive enteritis, there is still a dearth of relevant research. We performed extensive single-cell sequencing of colon crypts and immune cells in irradiated enteritis mice. We presented the significant differences in cell clusters of mice intestinal crypts after radiation, and further identified the significantly differentially expressed gene PLAC8, a novel specific marker of radio-inflammatory damage in Goblet cells. Our results further confirm the plasticity of Goblet cells in radiation enteritis, and the upregulation of the PLAC8 gene promotes Goblet cells' involvement in epithelial regeneration, providing new insights into the molecular pathways of radiation injury-induced regeneration and fundamental data for the treatment of radiation enteritis.

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“…Radiation toxicities, such as oral mucositis and radiation caries in Head & Neck cancer patients [ 66 , 67 ] and radiation enteritis in cancer patients receiving abdominal or thoracic radiation [ 68 , 69 , 70 ], are common and impact the patients’ quality of life. Additionally, toxicity to normal tissue may force reduction of radiotherapy dosage thereby impairing overall efficacy.…”

Section: Discussionmentioning

confidence: 99%

Opaganib Protects against Radiation Toxicity: Implications for Homeland Security and Antitumor Radiotherapy

Maines

Schrecengost

Zhuang

et al. 2022

IJMS

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Exposure to ionizing radiation (IR) is a lingering threat from accidental or terroristic nuclear events, but is also widely used in cancer therapy. In both cases, host inflammatory responses to IR damage normal tissue causing morbidity and possibly mortality to the victim/patient. Opaganib, a first-in-class inhibitor of sphingolipid metabolism, has broad anti-inflammatory and anticancer activity. Opaganib elevates ceramide and reduces sphingosine 1-phosphate (S1P) in cells, conditions that increase the antitumor efficacy of radiation while concomitantly suppressing inflammatory damage to normal tissue. Therefore, opaganib may suppress toxicity from unintended IR exposure and improve patient response to chemoradiation. To test these hypotheses, we first examined the effects of opaganib on the toxicity and antitumor activity of radiation in mice exposed to total body irradiation (TBI) or IR with partial bone marrow shielding. Oral treatment with opaganib 2 h before TBI shifted the LD75 from 9.5 Gy to 11.5 Gy, and provided substantial protection against gastrointestinal damage associated with suppression of radiation-induced elevations of S1P and TNFα in the small intestines. In the partially shielded model, opaganib provided dose-dependent survival advantages when administered 4 h before or 24 h after radiation exposure, and was particularly effective when given both prior to and following radiation. Relevant to cancer radiotherapy, opaganib decreased the sensitivity of IEC6 (non-transformed mouse intestinal epithelial) cells to radiation, while sensitizing PAN02 cells to in vitro radiation. Next, the in vivo effects of opaganib in combination with radiation were examined in a syngeneic tumor model consisting of C57BL/6 mice bearing xenografts of PAN02 pancreatic cancer cells and a cross-species xenograft model consisting of nude mice bearing xenografts of human FaDu cells. Mice were treated with opaganib and/or IR (plus cisplatin in the case of FaDu tumors). In both tumor models, the optimal suppression of tumor growth was attained by the combination of opaganib with IR (± cisplatin). Overall, opaganib substantially protects normal tissue from radiation damage that may occur through unintended exposure or cancer radiotherapy.

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Research progress on the mechanism of radiation enteritis

Cited by 15 publications

References 71 publications

Blocking TRAIL-DR5 signaling pathway with soluble death receptor 5 fusion protein mitigates radiation-induced injury

Blocking TRAIL-DR5 signaling pathway with soluble death receptor 5 fusion protein mitigates radiation-induced injury

Single Cell Atlas of Murine Crypt with Acute Radiation Enteritis

Opaganib Protects against Radiation Toxicity: Implications for Homeland Security and Antitumor Radiotherapy

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