Effects of dimethyl diphenyl bicarboxylate on the metabolism and hepatotoxicity of aflatoxin B1 in rats.
OBJECTIVE
To study the effect of antihepatitis drug, dimethyl diphenyl bicarboxylate (DDB) on the metabolism and hepatotoxicity of aflatoxin B1(AFB1) in rats.


METHODS
Rats 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.


RESULTS
DDB (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.


CONCLUSIONS
The results indicate that DDB protected rats against AFB1 hepatotoxicity by increasing the detoxifying metabolism of AFB1 in the liver.
Lu
Hong
H
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Li
Yan
Y
D016604:Aflatoxin B1 / Q000493:pharmacokinetics / Q000633:toxicity*; D016607:Aflatoxin M1 / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004149:Dioxoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats
D004149:Dioxoles; D020011:Protective Agents; D016607:Aflatoxin M1; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase