胃肠道毒性是腹部盆腔肿瘤放疗的主要副作用之一。研究显示，丁香醚醛（PAH）具有抗氧化、抗炎、抗微生物和抗肿瘤作用。本研究旨在确定PAH是否对放射性肠损伤具有辐射防护效应，并探索其潜在机制。将C57BL/6J小鼠灌胃PAH 7天后，暴露于单剂量13Gy的X射线全腹部照射（total abdominal irradiation, TAI）。PAH治疗延长了小鼠的存活时间，促进了隐窝细胞的生存，减轻了辐射诱导的DNA损伤，并缓解了被照射小鼠的肠道屏障损伤。PAH在肠隐窝器官样体和人类肠上皮细胞（HIEC-6）中也显示出辐射防护效应。PAH介导的辐射防护与核因子红细胞-相关因子2（Nrf2）的上调、抗氧化途径的激活以及铁死亡的抑制有关。值得注意的是，Nrf2抑制剂ML385的治疗使PAH的保护效应消失，表明Nrf2的激活对于PAH的活性是必要的。PAH抑制电离辐射（IR）诱导的铁死亡并通过激活Nrf2信号通路减轻辐射损伤。因此，PAH是一种有前景的IR诱导的肠道损伤治疗策略。© 2023 Wiley-VCH GmbH.

Gastrointestinal 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.C57BL/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.PAH 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.© 2023 Wiley-VCH GmbH.