Effects of bicyclol on the activity and expression of CYP450 enzymes of rats after partial hepatectomy / 药学学报

ABSTRACT

The present study was performed to investigate the effect of bicyclol on hepatic microsomal cytochrome P450 (CYP) activity, as well as gene and protein expressions in rats after partial hepatectomy (PH). Bicyclol (300 mg x kg(-1)) was given to rats subjected to 70% hepatectomy three times before operation. At 6 and 48 h after PH, blood and liver tissue samples were collected for the measurement of serum alanine aminotransferase (ALT), hepatic microsomal malondialdehyde (MDA) and total hepatic CYP content. The activities of four CYP isozymes were detected with liquid chromatography-mass spectrometry (LC-MS) and the gene and protein expressions were determined by RT-PCR and Western blotting assay. As a result, bicyclol pretreatment markedly inhibited the elevation of serum ALT and hepatic microsomal MDA, and prevented the decrease of total hepatic CYP content in PH rats. In addition, bicyclol significantly attenuated the reduction of CYP2C6 activity and mRNA expression, as well as the reduction of CYP2C11 activity in PH rats. Bicyclol can inhibit the decrease of CYP3A1/2 activity, and up-regulate the mRNA and protein expressions of CYP3A1 and CYP2E1. These results showed that bicyclol pretreatment might ameliorate abnormality in CYP450 isoforms during liver regeneration after PH, and this protective effect was likely due to its anti-oxidative property and enzyme induction.