Deoxynivalenol induces testicular ferroptosis by regulating the Nrf2/ System Xc-/GPX4 axis

文献类型： 外文期刊

第一作者： Yang, Xu

作者： Yang, Xu;Huang, Tingyu;Chen, Yunhe;Chen, Fengjuan;Liu, Yu;Wang, Youshuang;Song, Wenxi;Zhang, Juntao;Zhang, Cong;Zhang, Cong;Jiang, Yibao;Wang, Fangyu;Zhang, Cong;Zhang, Cong

作者机构：

关键词： Deoxynivalenol; Testis; Ferroptosis; Nrf2 pathway; Lipid peroxidation

期刊名称：FOOD AND CHEMICAL TOXICOLOGY （ 影响因子：4.3； 五年影响因子：5.1 ）

ISSN： 0278-6915

年卷期： 2023 年 175 卷

页码：

收录情况： SCI

摘要： Deoxynivalenol (DON) is the most common mycotoxin contaminant in food and feed. DON accumulation in food chain severely threatens human and animal health due to the toxic effects on the reproduction system. However, the underlying mechanism of DON on male reproductive dysfunction is still in debate and there is little infor-mation about whether DON triggers testicular ferroptosis. In this study, male C57BL/6 mice were divided into 4 groups and treated by oral gavage with 0, 0.5, 1.0, 2.0 mg/kg BW DON for 28 days. Firstly, we proved that male reproduction dysfunction was induced by DON through assessing testicular histopathology, serum testosterone level as well as blood-testis barrier integrity. Then, we verified ferroptosis occurred in DON-induced testicular dysfunction model through disrupting iron homeostasis, increasing lipid peroxidation and inhibiting system Xc/ Gpx4 axis. Notably, the present data showed DON reduced antioxidant capacity via blocking Nrf2 pathway to lead to the further weakness of ferroptosis resistance. Altogether, these results indicated that DON caused mice testicular ferroptosis associated with inhibiting Nrf2/System Xc-/GPx4 axis, which provided that maintaining testicular iron homeostasis and activating Nrf2 pathway may be a potential target for alleviating testicular toxicity of DON in the future.

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