文献类型：期刊文献

英文题名：Role of NF-kappa B signaling pathway in hexavalent chromium-induced hepatotoxicity

作者：Shen, Jiayuan[1];Kom, Merveille Chancelle[2];Huang, Huarong[3];Fu, Guoquan[2];Xie, Yixia[2];Gao, Yue[2];Tang, Yaxin[2];Yan, Junyan[2,5];Jin, Lifang[2,4,5]

机构：[1]Shaoxing Univ, Affiliated Hosp, Dept Pathol, Shaoxing, Peoples R China;[2]Shaoxing Univ, Sch Life Sci, Shaoxing, Peoples R China;[3]Hangzhou Normal Univ, Coll Life & Environm Sci, Hangzhou, Peoples R China;[4]Zhejiang Sci Tech Univ, Shaoxing Acad Biomed, Shaoxing, Peoples R China;[5]Shaoxing Univ, Sch Life Sci, Shaoxing 312000, Peoples R China

年份：0

外文期刊名：ENVIRONMENTAL TOXICOLOGY

收录：SCI-EXPANDED(收录号：WOS:000943856600001)、、EI(收录号：20231213782220)、Scopus(收录号：2-s2.0-85150417201)、WOS

基金：ACKNOWLEDGMENTS The project was supported by Open Fund of Shaoxing Academy of Biomedicine of Zhejiang Sci-Tech University (SXAB202015) and Zhejiang Province Science and Technology Project of China (2018C37105).

语种：英文

外文关键词：hepatotoxicity; hexavalent chromium Cr (VI); N-acetyl-L-cysteine (NAC); NF-kappa B pathway; RNA-seq

外文摘要：Hexavalent chromium Cr (VI) is a primary human carcinogen with damaging toxic effects on multiple organs. Cr (VI) exposure can induce hepatotoxicity through oxidative stress, but its exact mechanism of action was still unclear. In our study, a model of acute Cr (VI) induced liver injury was established by exposing mice to different concentrations (0, 40, 80, and 160 mg/kg) of Cr (VI); RNA-seq was used to characterize changes in liver tissue transcriptome of C57BL/6 mice after exposing to 160 mg/kg Bw of Cr (VI). Changes in liver tissue structures, proteins, and genes were observed by hematoxylin and eosin (H & E), western blot, immunohistochemistry and RT-PCR. After Cr (VI) exposure, abnormal liver tissue structure, hepatocyte injury, and hepatic inflammatory response were observed in mice in a dose-dependent manner. RNA-seq transcriptome results indicated that oxidative stress, apoptosis, and inflammatory response pathways were increased after Cr (VI) exposure; KEGG pathway analysis found that activation of NF-kappa B signaling pathway was significantly upregulated. Consistent with the RNA-seq results, immunohistochemistry showed that Cr (VI) exposure resulted in infiltrating of Kupffer cells and neutrophils, increasing expression of inflammatory factors (TNF-alpha, IL-6, IL-1 beta), and activating of NF-kappa B signaling pathways (p-IKK alpha/beta and p-p65). However, ROS inhibitor, N-acetyl-L-cysteine (NAC), could reduce infiltration of Kupffer cells and neutrophils and expression of inflammatory factors. Besides, NAC could inhibit NF-kappa B signaling pathway activation, and alleviate Cr (VI)-induced liver tissue damage. Our findings strongly suggested that inhibition of ROS by NAC might help in the development of new strategies for Cr (VI)-associated liver fibrosis. Our findings revealed for the first time that Cr (VI) induced liver tissue damage through the inflammatory response mediated by the NF-kappa B signaling pathway, and inhibition of ROS by NAC might help in the development of new strategies for Cr (VI)-associated hepatotoxicity.