Glutathione Conjugation and Protein Adduction by Environmental Pollutant 2,4-Dichlorophenol In Vitro and In Vivo.,Chemical Research in Toxicology

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Glutathione Conjugation and Protein Adduction by Environmental Pollutant 2,4-Dichlorophenol In Vitro and In Vivo.
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2020-08-11 , DOI: 10.1021/acs.chemrestox.0c00118
Qingmei Li ₁ , Wei Li ₁ , Jiaxing Zhao ₁ , Xiucai Guo ₁ , Qian Zou ₁ , Zixin Yang ₁ , Ruixue Tian ₁ , Ying Peng ₁ , Jiang Zheng _{1,

2,

3}

Affiliation

2,4-Dichlorophenol (2,4-DCP), an environmental pollutant, was reported to cause hepatotoxicity. The biochemical mechanisms of 2,4-DCP induced liver injury remain unknown. The present study showed that 2,4-DCP is chemically reactive and spontaneously reacts with GSH and bovine serum albumin to form GSH conjugates and BSA adducts. The observed conjugation/adduction apparently involved the addition of GSH and departure of chloride via the ipso substitution pathway. Two biliary GSH conjugates and one urinary N-acetyl cysteine conjugate were observed in rats given 2,4-DCP. The N-acetyl cysteine conjugate was chemically synthesized and characterized by mass spectrometry and NMR. As expected, 2,4-DCP was found to modify hepatic protein at cysteine residues in vivo by the same chemistry. The observed protein adduction reached its peak at 15 min and revealed dose dependency. The new findings allowed us to better understand the mechanisms of the toxic action of 2,4-DCP.

中文翻译：

环境污染物 2,4-二氯苯酚在体外和体内的谷胱甘肽结合和蛋白质加成。

据报道，2,4-二氯苯酚 (2,4-DCP) 是一种环境污染物，会导致肝毒性。2,4-DCP 诱导肝损伤的生化机制尚不清楚。本研究表明，2,4-DCP 具有化学反应性，可自发地与 GSH 和牛血清白蛋白反应，形成 GSH 结合物和 BSA 加合物。观察到的结合/加成显然涉及通过ipso替代途径添加 GSH 和离开氯化物。在给予 2,4-DCP 的大鼠中观察到两种胆汁 GSH 结合物和一种尿N-乙酰半胱氨酸结合物。该ñ-乙酰半胱氨酸缀合物是化学合成的，并通过质谱和核磁共振进行表征。正如预期的那样，发现 2,4-DCP 在体内通过相同的化学修饰半胱氨酸残基处的肝脏蛋白质。观察到的蛋白质加成在 15 分钟时达到峰值，并显示出剂量依赖性。新发现使我们能够更好地了解 2,4-DCP 的毒性作用机制。

更新日期：2020-09-21

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