2-Naphthalenemethanol participates in metabolic activation of 2-methylnaphthalene

Kunna Li; Ying Zou; Yang Wang; Mengyue Zhou; Jing Li; Rong Tan; Shiyu Zhang; Weiwei Li; Jiang Zheng

doi:10.1080/00498254.2022.2079022

2-Naphthalenemethanol participates in metabolic activation of 2-methylnaphthalene

Xenobiotica. 2022 Apr;52(4):360-369. doi: 10.1080/00498254.2022.2079022. Epub 2022 May 30.

Authors

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}

Affiliations

¹ State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, Guiyang, P R China.
² School of Pharmacy, Guizhou Medical University, Guiyang, P R China.
³ Key Laboratory of Environmental Pollution, Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, P R China.
⁴ Wuya of Innovation, Shenyang Pharmaceutical University, Shenyang, P R China.

PMID: 35575452
DOI: 10.1080/00498254.2022.2079022

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.

Keywords: 2-methylnaphthalene; 2-naphthalenemethanol; P450 enzymes; metabolic activation; sulfotransferases.

MeSH terms

Activation, Metabolic
Animals
Glutathione / metabolism
Mice
Microsomes, Liver* / metabolism
Naphthalenes* / metabolism

Substances

Naphthalenes
2-naphthalenemethanol
Glutathione
2-methylnaphthalene