State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, P R China.
School of Pharmacy, Guizhou Medical University, Guiyang, P R China.
Xenobiotica. 2022 Apr;52(4):360-369. doi: 10.1080/00498254.2022.2079022. Epub 2022 May 30.
2-Methylnaphthalene (2-MN) is an environmental pollutant. Studies have shown that 2-MN is teratogenic, carcinogenic, and cytotoxic. However, the mechanisms of 2-MN induced toxicities remain unclear.This study aimed to characterise reactive metabolites of 2-MN, to define the metabolic pathway, and to determine the enzymes participating in the metabolic activation.A hydroxylation metabolite of 2-MN, 2-naphthalenemethanol (2-NM), was observed in 2-MN-containing mouse liver microsomes.A glutathione (GSH) conjugate was detected in mouse S9 incubations fortified with 2-MN and GSH. A GSH conjugate and an NAC conjugate were found in mouse liver and urine, respectively, in animals given 2-MN. Hepatic protein covalent binding derived from 2-NM was observed in animals administered 2-MN.Cytochrome P450 enzymes and sulfotransferases participated in the metabolic activation of 2-MN.
2-甲基萘（2-MN）是一种环境污染物。研究表明，2-MN 具有致畸性、致癌性和细胞毒性。然而，2-MN 诱导毒性的机制尚不清楚。本研究旨在描述 2-MN 的反应代谢物，确定代谢途径，并确定参与代谢激活的酶。在含有 2-MN 的小鼠肝微粒体中观察到 2-MN 的羟化代谢物 2-萘甲醇（2-NM）。在添加 2-MN 和 GSH 的小鼠 S9 孵育中检测到谷胱甘肽（GSH）缀合物。在给予 2-MN 的动物的肝脏和尿液中分别发现了 GSH 缀合物和 NAC 缀合物。在给予 2-MN 的动物中观察到来源于 2-NM 的肝蛋白共价结合。细胞色素 P450 酶和磺基转移酶参与了 2-MN 的代谢激活。
