Hong Lu1, Yan Li. 1. Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100050, China.
Abstract
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.
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 AFB1hepatotoxicity 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 AFB1hepatotoxicity by increasing the detoxifying metabolism of AFB1 in the liver.
Authors: S Gratz; M Täubel; R O Juvonen; M Viluksela; P C Turner; H Mykkänen; H El-Nezami Journal: Appl Environ Microbiol Date: 2006-09-15 Impact factor: 4.792
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