2-Naphthalenemethanol participates in metabolic activation of 2-methylnaphthalene

Abstract

1. 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.

2. 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.

3. A hydroxylation metabolite of 2-MN, 2-naphthalenemethanol (2-NM), was observed in 2-MN-containing mouse liver microsomes.

4. 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.

5. Cytochrome P450 enzymes and sulfotransferases participated in the metabolic activation of 2-MN.

Keywords:

• 2-methylnaphthalene
• 2-naphthalenemethanol
• P450 enzymes
• sulfotransferases
• metabolic activation

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant number: U1812403].