Metabolic Activation and Cytotoxicity of Fungicide Carbendazim Mediated by CYP1A2.
J Agric Food Chem
; 70(13): 4092-4101, 2022 Apr 06.
Article
in En
| MEDLINE
| ID: mdl-35316061
ABSTRACT
Carbendazim (CBZ) is a broad-spectrum fungicide widely used in many nations for foliar spray as well as seed and soil treatment. The resulting contamination and environmental pollution have been drawing public attention. In particular, CBZ was reported to cause liver damage in rats and zebrafish, and the mechanisms of its toxicity have not been clarified. The purposes of this study were to investigate the metabolic activation of CBZ and to determine a possible role of the reactive metabolites in CBZ-induced liver injury reported. One oxidative metabolite (M1), one glutathione conjugate (M2), and one N-acetyl cysteine conjugate (M3) were detected in human and rat liver microsomal incubations fortified with glutathione or N-acetyl cysteine after exposure to CBZ. CYP1A2 was the major enzyme responsible for the metabolic activation of CBZ. Biliary M2 and urinary M3 were detected in rats treated with CBZ. CBZ-derived protein adduction was found in cultured rat primary hepatocytes treated with CBZ. The increase of administration concentration intensified not only the cytotoxicity but also protein adduction induced by CBZ, suggesting a correlation of the cytotoxicity with the observed protein modification. The findings facilitate the understanding of the mechanisms of toxic action of CBZ.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Zebrafish
/
Cytochrome P-450 CYP1A2
Limits:
Animals
Language:
En
Journal:
J Agric Food Chem
Year:
2022
Document type:
Article