Affiliation:
1. State Key Laboratory of Radiation Medicine and Protection School of Radiation Medicine and Protection Medical College of Soochow University Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions Soochow University Suzhou Jiangsu 215123 China
2. The Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215004 China
3. Department of General Surgery The Affiliated Suqian Hospital of Xuzhou Medical University Suqian Jiangsu 223800 China
4. Department of Medical Oncology The First Affiliated Hospital of Soochow University Suzhou Jiangsu 215006 China
Abstract
ScopeGastrointestinal toxicity is one of the major side effects of abdominopelvic tumor radiotherapy. Studies have shown that perillaldehyde (PAH) has antioxidant, antiinflammatory, antimicrobial activity, and antitumor effects. This study aims to determine whether PAH has radioprotective effects on radiation‐induced intestinal injury and explore the underlying mechanisms.Methods and resultsC57BL/6J mice are gavaged with PAH for 7 days, then exposed to a single dose of 13 Gy X‐ray total abdominal irradiation (TAI). PAH treatment prolongs the survival time, promotes the survival of crypt cells, attenuates radiation‐induced DNA damage, and mitigates intestinal barrier damage in the irradiated mice. PAH also shows radioprotective effects in intestinal crypt organoids and human intestinal epithelial cells (HIEC‐6). PAH‐mediated radioprotection is associated with the upregulation of nuclear factor erythroid‐2 related factor 2 (Nrf2), activation of the antioxidant pathway, and inhibition of ferroptosis. Notably, treatment with the Nrf2 inhibitor ML385 abolishes the protective effects of PAH, indicating that Nrf2 activation is essential for PAH activity.ConclusionPAH inhibits ionizing radiation (IR)‐induced ferroptosis and attenuates intestinal injury after irradiation by activating Nrf2 signaling. Therefore, PAH is a promising therapeutic strategy for IR‐induced intestinal injury.
Funder
National Natural Science Foundation of China
Subject
Food Science,Biotechnology
Cited by
2 articles.
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