Effects of dimethyl diphenyl bicarboxylate on the metabolism and hepatotoxicity of aflatoxin B1 in rats.
- Author:
Hong LU
1
;
Yan LI
Author Information
- Publication Type:Journal Article
- MeSH: Aflatoxin B1; pharmacokinetics; toxicity; Aflatoxin M1; metabolism; Alanine Transaminase; blood; Animals; Aspartate Aminotransferases; blood; Biotransformation; Chemical and Drug Induced Liver Injury; etiology; metabolism; prevention & control; Cytochrome P-450 Enzyme System; metabolism; Dioxoles; therapeutic use; Disease Models, Animal; Male; Microsomes, Liver; metabolism; Protective Agents; therapeutic use; Rats
- From: Acta Pharmaceutica Sinica 2002;37(10):753-757
- CountryChina
- Language:English
-
Abstract:
AIMTo study the effect of antihepatitis drug, dimethyl diphenyl bicarboxylate (DDB) on the metabolism and hepatotoxicity of aflatoxin B1(AFB1) in rats.
METHODSRats were given orally DDB 300 mg.kg-1.d-1 for 3 days and then injected intraperitioneally with AFB1 1.5 mg.kg-1. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were examined 16 hours after the injection of AFB1. The in vitro metabolism of AFB1 by DDB-pretreated rat liver microsome was investigated by HPLC assay.
RESULTSDDB (300 mg.kg-1) pretreatment provided significant protection against AFB1 hepatotoxicity as evidenced by the decrease of AFB1-elevated serum marker enzymes in rats. Pretreatment with DDB was shown to slightly increase the level of AFM1, the less toxic metabolite. DDB significantly increased the liver cytochrome P450 content, P450 isozyme 2B1-mediated 7-pentoxyresorufin O-dealkylase (PROD) activity, cytosolic glutahione (GSH) level and GSH S-transferase (GST) activities. In addition, DDB slightly increased P450 isozymes, 3A-mediated erythromycin-demethylase and 1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activities.
CONCLUSIONThe results indicate that DDB protected rats against AFB1 hepatotoxicity by increasing the detoxifying metabolism of AFB1 in the liver.
