CYP2E1 mediated deoxynivalenol-induced hepatocyte toxicity by regulating ferroptosis

被引:3
|
作者
Mo, Qigui [1 ]
Song, Chenchen [2 ]
Hua, Yu [1 ]
Wang, Wei [2 ]
Liu, Aimei [1 ]
机构
[1] Hubei Univ Sci & Technol, Med Res Inst, Xianning Med Coll, Hubei Key Lab Diabet & Angiopathy, Xianning 437100, Peoples R China
[2] Hubei Univ Sci & Technol, Xianning Med Coll, Sch Basic Med Sci, Xianning 437100, Peoples R China
关键词
Deoxynivalenol; Hepatocyte toxicity; Ferroptosis; OXIDATIVE STRESS; MYCOTOXINS; EXPRESSION; MECHANISM; DAMAGE;
D O I
10.1016/j.tox.2024.153923
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Deoxynivalenol (DON), one of the most common mycotoxins in food and feed, can cause acute and chronic liver injury, posing a serious health risk to humans and animals. One of the important manifestations of DON-induced hepatotoxicity is ferroptosis. It has been reported that CYP2E1 can mediated ferroptosis, but the role of DONinduced CYP2E1 in DON-induced ferroptosis in hepatocytes is unknown. In the present study, we observed that DON significantly increased the expression of CYP2E1 and decreased the expression of the ferroptosis inhibitory proteins GPX4 and SLC7A11, as well as GCLC and NQO1. This resulted in an increase in the levels of cell lipid ROS and FeII, 4-HNE, which ultimately led to cell ferroptosis. Notably, knockdown of CYP2E1 resulted in an increase in DON-induced low levels of GPX4 and SLC7A11, a decrease in DON-induced high levels of lipid ROS, FeII and cell secreted 4-HNE, thus ameliorating cell ferroptosis. Moreover, the ferroptosis inhibitor ferrostatin-1 was observed to antagonise the cell growth inhibitory toxicity induced by DON exposure. This was achieved by blocking the increase in lipid ROS and FeII overload, which in turn reduced the extent of ferroptosis and increased IGF-1 protein expression. In conclusion, the present study demonstrated that CYP2E1 played a regulatory role in DON-induced ferroptosis in hepatocytes. Targeting ferroptosis may prove an effective strategy for alleviating DON-induced cell growth retardation toxicity. These findings provided a potential target and strategies to mitigate DON hepatotoxicity in the future.
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页数:9
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