封堵器
生物
肠道菌群
脂肪变性
细胞生物学
生物化学
内分泌学
紧密连接
作者
Quanwei Li,Pengyi Guo,Shaofeng Wang,Le Su,Tingyu Liang,Wenli Yu,Jianying Guo,Qing Yang,Zhaoxin Tang,Jianzhao Liao
标识
DOI:10.1016/j.scitotenv.2023.169642
摘要
Terbuthylazine (TBA) is a widely prevalent pesticide pollutant, which is a global concern due to its environmental residual. However, the toxic mechanism of TBA have not been fully solved. Here, we explored that TBA exposure disrupts the intestinal flora and aggravated disturbance of mitochondrial quality control and PANapoptosis in hepatocytes via gut-liver axis. Our findings demonstrated that TBA exposure induced significant damage to the jejunum barrier, evidenced by a marked decrease in the expression of Occludin and ZO-1. Moreover. TBA led to intestinal microflora disorder, manifested as the decreased abundance of Firmicutes, and increased abundance of the Nitrospirota, Chloroflexi, Desulfobacterota, Crenarchaeota, Myxococcota, and Planctomycetota. Meanwhile, intestinal microflora disorder affected the biological processes of lipid metabolism and cell growth and death of hepatocytes by RNA-Seq analysis. Furthermore, TBA could induced mitochondrial quality control imbalance, including mitochondrial redox disorders, lower activity of mitochondrial fusion and biogenesis decrease, and increasing level of mitophagy. Subsequently, TBA significantly increased expression levels of pyroptosis, apoptosis and necroptosis-related proteins. In general, these results demonstrated the underlying mechanisms of TBA-induced hepatotoxicity induced via the gut–liver axis, which provides a theoretical basis for further research of ecotoxicology of TBA.
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