Dose-related effect of aflatoxin B1 on liver drug metabolizing enzymes in rabbit.
Toxicology
; 108(1-2): 39-48, 1996 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-8644116
ABSTRACT
The effects of chronic administration of aflatoxin B1 (AFB1) on liver drug metabolism enzymes were measured in New Zealand rabbits divided into three groups of 5 animals, each receiving over 5 days either arabic gum or AFB1 in arabic gum at a daily oral dose of 0.05 or 0.10 mg/kg. These treatments did not lead to any lethality in any of the treated groups, but the body weight gain was altered. Biochemical exploration of plasma components revealed a dose-dependent hepatotoxicity characterized by cytolysis and cholestasis. At 0.10 mg/kd/day of AFB1, significant decreases were observed in total liver microsomal cytochrome P450, several P450-dependent monooxygenase activities, all individual P450 isoenzymes levels analysed by Western-blotting and glutathione S-transferase activities. By contrast, at 0.05 mg/kg/day of AFB1, even though total cytochrome P450 was decreased by 30%, only P450 1A1 and 3A6 isoenzymes, and aniline hydroxylation, pentoxyresorufin O-depentylation, aminopyrine, erythromycin, ethylmorphine and dimethylnitrosamine N-demethylations were affected. In the same animal group, the only glutathione S-transferase accepting CDNB (1-chloro-2,4-dinitrobenzene) as substrate was decreased by 22%. UDP-glucuronyltransferase accepting p-nitrophenol as substrate was increased in both groups of animals (33-62%). The mechanisms that could contribute to the observed changes in drug metabolizing enzymes are discussed.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinógenos
/
Aflatoxina B1
/
Inibidores Enzimáticos
/
Fígado
Limite:
Animals
Idioma:
En
Revista:
Toxicology
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
França