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Effects of bicyclol on aflatoxin B1 metabolism and hepatotoxicity in rats
1Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100050, China.
Aim:
To study the effect of new antihepatitis drug, bicyclol, on the metabolism and hepatotoxicity of aflatoxin B1 (AFB1) in rats.
Methods:
Rats were given bicyclol 300 mg/kg/d ig for 3 d and then injected ip with AFB1 1.5 mg/kg. Liver damages were examined 16 h after ip AFB1. The in vitro metabolism of AFB1 by bicyclol-pretreated liver microsomes was investigated by HPLC assay.
Results:
Bicyclol (300 mg/kg/d for 3 d) pretreatment provided protection against AFB1 hepatotoxicity as evidenced by the decrease of AFB1-elevated serum aminotransferase and hepatic malondialdehyde in rats. Bicyclol pretreatment slightly increased the production of the less toxic metabolite aflatoxin Q1. Bicyclol increased liver cytochrome P450 content, CYP 2B1-mediated 7-pentoxyresorufin O-dealkylase (PROD) activity, cytosolic glutathione (GSH) level, and GSH S-transferase (GST) activities. Moreover, bicyclol increased CYP 3A-mediated erythromycin-demethylase and CYP 1A-mediated 7-ethoxyresorufin O-deethylase (EROD) activities.
Conclusion:
Bicyclol protected rats against AFB1 hepatotoxicity by increasing the detoxifying metabolism of AFB1 in the liver.