Glutathione conjugation and protein modification resulting from metabolic activation of pesticide metalaxyl in vitro and in vivo.
Pestic Biochem Physiol
; 196: 105606, 2023 Nov.
Article
de En
| MEDLINE
| ID: mdl-37945228
ABSTRACT
Metalaxyl (MTL), a germicidal agent, is widely used in agriculture. Due to the biological amplification effect, MTL entering the ecological environment would result in a threat to human health through the food chain. MTL is reportedly accumulated in liver. The objectives of the study included investigating the metabolic activation of MTL in liver and defining the mechanisms participating in the hepatotoxicity of MTL. The corresponding glutathione (GSH), N-acetylcysteine (NAC) conjugate, and cysteine conjugates were observed in liver microsomes, prepared from liver tissues of mice, containing MTL and GSH, NAC or cysteine. These conjugates were also detected in urine and bile of rats receiving MTL. Apparently, MTL was biotransformed to a quinone imine intermediate dose-dependently attacking the thiols and cysteine residues of protein. The bioactivation of MTL required cytochrome P450 enzymes, and CYP3A dominated the bio-activation of MTL.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pesticides
Limites:
Animals
/
Humans
Langue:
En
Journal:
Pestic Biochem Physiol
Année:
2023
Type de document:
Article