Remission of copper-induced liver injury through the PXR/NF-kB signaling pathway: The effects of dietary curcumin supplementation in largemouth bass ( Micropterus salmoides) )

文献类型： 外文期刊

第一作者： Li, Hongyan

作者： Li, Hongyan;Fu, Yiying;Gong, Wangbao;Wang, Guangjun;Li, Zhifei;Tian, Jingjing;Zhang, Kai;Yu, Ermeng;Xia, Yun;Xie, Wenping;Xie, Jun;Li, Hongyan;Fu, Yiying;Gong, Wangbao;Wang, Guangjun;Li, Zhifei;Tian, Jingjing;Zhang, Kai;Yu, Ermeng;Xia, Yun;Xie, Wenping;Xie, Jun;Li, Hongyan

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关键词： PXR//NF-kb signaling; Cu exposure; Curcumin; Liver injury

期刊名称：ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY （ 影响因子：6.1； 五年影响因子：6.4 ）

ISSN： 0147-6513

年卷期： 2024 年 285 卷

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收录情况： SCI

摘要： The pregnane X receptor (PXR)/nuclear factor-kB (NF-kB) signaling pathway plays a critical role in regulating toxin-induced inflammation and apoptosis in mammals. Whether dietary curcumin (CUR) can prevent copper (Cu)-induced liver injury via this signaling pathway remains to be established in aquatic animals. Juvenile largemouth bass (Micropterus salmoides) were exposed to dietary Cu and CUR treatments for 8 weeks. The results showed that chronic Cu exposure induced oxidative stress, causing liver function damage and liver injury. Cu exposure stimulated inflammation by regulating nf-kb and pro-inflammatory genes such as tnf alpha and il-1 beta and promoted apoptotic signals in the liver by modulating bcl2 and casp3 mRNA levels. In addition, Pearson correlation analysis verified that inflammatory and apoptotic responses were important indicators of Cu-induced liver injury. CUR attenuated stress responses by enhancing the antioxidant system. Importantly, CUR significantly stimulated PXR mRNA and protein levels in the Cu + CUR group and suppressed NF-kappa B activation to inhibit the inflammatory and apoptotic signaling cascade. These results suggest that CUR may be an effective activator of PXR in teleost fishes, exerting cytoprotective effects on Cu-induced liver injury via a PXR-mediated NF-kappa B repression mechanism. In conclusion, this study is the first to demonstrate that CUR may act as a potent PXR ligand that exerts hepatoprotective effects against Cu-induced liver injury. The findings shed light on the specific regulatory role of the PXR/NF-kappa B signaling pathway in liver pathogenesis and its potential as a therapeutic target in teleost fishes.

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