Xenobiotica ( IF 1.3 ) Pub Date : 2022-05-30 , DOI: 10.1080/00498254.2022.2079022 Kunna Li 1, 2 , Ying Zou 1, 2 , Yang Wang 1, 2 , Mengyue Zhou 1, 2 , Jing Li 1, 2 , Rong Tan 1, 2 , Shiyu Zhang 1, 2 , Weiwei Li 1, 2 , Jiang Zheng 1, 2, 3, 4
Abstract
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.
中文翻译:
2-萘甲醇参与2-甲基萘的代谢活化
摘要
2-甲基萘 (2-MN) 是一种环境污染物。研究表明,2-MN 具有致畸、致癌和细胞毒性。然而,2-MN 诱导毒性的机制仍不清楚。
本研究旨在表征 2-MN 的反应性代谢物,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 的羟基化代谢物 2-萘甲醇 (2-NM)。
在用 2-MN 和 GSH 强化的小鼠 S9 孵育中检测到谷胱甘肽 (GSH) 缀合物。在给予 2-MN 的动物中,分别在小鼠肝脏和尿液中发现了 GSH 偶联物和 NAC 偶联物。在给予 2-MN 的动物中观察到源自 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。