Tang Lin-Feng, Ma Xiaoming, Xie Li-Wei, Zhou Hao, Yu Jiahua, Wang Zhen-Xin, Li Ming
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.
The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, China.
Mol Nutr Food Res. 2023 Oct;67(19):e2300232. doi: 10.1002/mnfr.202300232. Epub 2023 Sep 1.
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.
胃肠道毒性是腹盆腔肿瘤放疗的主要副作用之一。研究表明，紫苏醛（PAH）具有抗氧化、抗炎、抗菌活性以及抗肿瘤作用。本研究旨在确定PAH对辐射诱导的肠道损伤是否具有辐射防护作用，并探索其潜在机制。
给C57BL/6J小鼠灌胃PAH 7天，然后对其进行单次13 Gy的全腹X射线照射（TAI）。PAH治疗可延长受照射小鼠的存活时间，促进隐窝细胞存活，减轻辐射诱导的DNA损伤，并减轻肠道屏障损伤。PAH在肠道隐窝类器官和人肠上皮细胞（HIEC-6）中也显示出辐射防护作用。PAH介导的辐射防护作用与核因子红细胞2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，用Nrf2抑制剂ML385处理可消除PAH的保护作用，这表明Nrf2激活对PAH的活性至关重要。
PAH通过激活Nrf2信号通路抑制电离辐射（IR）诱导的铁死亡，并减轻照射后的肠道损伤。因此，PAH是一种有前景的治疗IR诱导的肠道损伤的策略。
