2-Naphthalenemethanol participates in metabolic activation of 2-methylnaphthalene

被引：2

作者：

Li, Kunna ^{[1
,2
]}

Zou, Ying ^{[1
,2
]}

Wang, Yang ^{[1
,2
]}

Zhou, Mengyue ^{[1
,2
]}

Li, Jing ^{[1
,2
]}

Tan, Rong ^{[1
,2
]}

Zhang, Shiyu ^{[1
,2
]}

Li, Weiwei ^{[1
,2
]}

Zheng, Jiang ^{[1
,2
,3
,4
]}

机构：

[1] Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guizhou Prov Key Lab Pharmaceut, Guiyang 550004, Guizhou, Peoples R China

[2] Guizhou Med Univ, Sch Pharm, Guiyang, Peoples R China

[3] Guizhou Med Univ, Key Lab Environm Pollut Monitoring & Dis Control, Minist Educ, Guiyang, Peoples R China

[4] Shenyang Pharmaceut Univ, Wuya Innovat, Shenyang 110016, Liaoning, Peoples R China

来源：

XENOBIOTICA | 2022年 / 52卷 / 04期

基金：

中国国家自然科学基金;

关键词：

2-methylnaphthalene; 2-naphthalenemethanol; P450; enzymes; sulfotransferases; metabolic activation; POLYCYCLIC AROMATIC-HYDROCARBONS; IRREVERSIBLE BINDING; TOXICITY; LIVER;

D O I：

10.1080/00498254.2022.2079022

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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.

引用

页码：360 / 369

页数：10

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