Perillaldehyde Mitigates Ionizing Radiation-Induced Intestinal Injury by Inhibiting Ferroptosis via the Nrf2 Signaling Pathway

IF 4.5 2区农林科学 Q1 FOOD SCIENCE & TECHNOLOGY Molecular Nutrition & Food Research Pub Date : 2023-09-01 DOI:10.1002/mnfr.202300232

Lin-Feng Tang, Xiaoming Ma, Li-Wei Xie, Hao Zhou, Jiahua Yu, Zhen-Xin Wang, Ming Li

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Abstract

Scope

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.

Methods and results

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.

Conclusion

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.

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紫苏醛通过Nrf2信号通路抑制铁下垂减轻电离辐射诱导的肠损伤

范围胃肠道毒性是腹腔肿瘤放射治疗的主要副作用之一。研究表明，紫苏醛具有抗氧化、抗炎、抗菌和抗肿瘤的作用。本研究旨在确定PAH是否对放射性肠损伤具有放射性保护作用，并探讨其潜在机制。方法和结果用PAH灌胃C57BL/6J小鼠7天，然后单次13Gy X射线全腹照射（TAI）。PAH处理延长了受辐射小鼠的存活时间，促进了隐窝细胞的存活，减轻了辐射诱导的DNA损伤，并减轻了肠道屏障损伤。PAH在肠隐窝类器官和人肠上皮细胞（HIEC-6）中也显示出放射性保护作用。PAH介导的放射性保护与核因子-红细胞2型相关因子2（Nrf2）的上调、抗氧化途径的激活和脱铁性贫血的抑制有关。值得注意的是，用Nrf2抑制剂ML385处理消除了PAH的保护作用，表明Nrf2活化对PAH活性至关重要。结论PAH通过激活Nrf2信号传导抑制电离辐射诱导的脱铁性贫血，减轻辐射后肠道损伤。因此，PAH是一种很有前途的治疗IR诱导的肠道损伤的策略。

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来源期刊

Molecular Nutrition & Food Research 工程技术-食品科技

CiteScore

8.70

自引率

1.90%

发文量

250

审稿时长

1.7 months

期刊介绍： Molecular Nutrition & Food Research is a primary research journal devoted to health, safety and all aspects of molecular nutrition such as nutritional biochemistry, nutrigenomics and metabolomics aiming to link the information arising from related disciplines: Bioactivity: Nutritional and medical effects of food constituents including bioavailability and kinetics. Immunology: Understanding the interactions of food and the immune system. Microbiology: Food spoilage, food pathogens, chemical and physical approaches of fermented foods and novel microbial processes. Chemistry: Isolation and analysis of bioactive food ingredients while considering environmental aspects.