In Vitro and In Vivo Metabolic Activation and Hepatotoxicity of Environmental Pollutant 2,6-Dimethylphenol,Chemical Research in Toxicology

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In Vitro and In Vivo Metabolic Activation and Hepatotoxicity of Environmental Pollutant 2,6-Dimethylphenol
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2022-05-18 , DOI: 10.1021/acs.chemrestox.2c00048
Mingyu Zhang ₁ , Yaodong Hu ₁ , Wei Li ₁ , Chen Sun ₁ , Chunjing Guan ₁ , Ying Peng ₁ , Jiang Zheng _{1,

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Affiliation

2,6-Dimethylphenol (2,6-DMP) is an environmental pollutant found in industrial wastewater. Exposure to 2,6-DMP is of increasing concern as it endangered reportedly some aquatic animals. In this study, we investigated the metabolic activation and hepatotoxicity of 2,6-DMP. 2,6-DMP was metabolized to an o-quinone methide intermediate in vitro and in vivo. The electrophilic metabolite was reactive to the sulfhydryl groups of glutathione, N-acetyl cysteine, and cysteine. NADPH was required for the formation of the reactive metabolite. The quinone methide intermediate reacted with cysteine residues to form hepatic protein adduction. A single dose of 2,6-DMP induced marked elevation of serum ALT and AST in mice. Both the protein adduction and hepatotoxicity of 2,6-DMP showed dose dependency.

中文翻译：

环境污染物2,6-二甲基苯酚的体外和体内代谢活化及肝毒性

2,6-二甲基苯酚 (2,6-DMP) 是一种在工业废水中发现的环境污染物。暴露于 2,6-DMP 越来越受到关注，因为据报道它会危及一些水生动物。在这项研究中，我们研究了 2,6-DMP 的代谢活化和肝毒性。2,6-DMP在体外和体内代谢为邻醌甲基化物中间体。亲电子代谢物与谷胱甘肽的巯基反应，N-乙酰半胱氨酸和半胱氨酸。NADPH 是反应性代谢物形成所必需的。醌甲基化物中间体与半胱氨酸残基反应形成肝蛋白加合物。单剂量的 2,6-DMP 诱导小鼠血清 ALT 和 AST 显着升高。2,6-DMP 的蛋白质加合和肝毒性均表现出剂量依赖性。

更新日期：2022-05-18

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