| Objective: To study the effects of columbin on the catalytic activities and the expression of hepatic cytochrome P450 (CYP450) isozymes at protein and mRNA levels in experimental type 2 diabetic rats. Methods: An experimental type 2 diabetes mellitus rat model was induced by feeding rats with diet of high fat and high sugar and injecting them intraperitoneally with streptozotocin (STZ, 30 mg/kg), then eighteen type 2 diabetic rats were equally randomized into 3 groups: a model control group, a low dose columbin group (25 mg/kg/d, ig) and a high dose columbin group (50 mg/kg/d, ig). At the end of the fourth week treatment with columbin, the rats were sacrificed about 2 h later after the last dose. Livers were harvested and microsomes were prepared and analyzed for total CYP450 content and enzyme activities. Total RNA was also isolated and the mRNA levels of various CYPs were determined by quantitative RT-PCR with Taqman MGB probes. In addition, the protein levels of CYP2E1 were measured by Western blotting. Results: The obvious changes of liver CYP450 have been found in this investigation.â‘ While no significant changes were detected on liver micorsomes CYP450 content in model control group (P>0.05), the CYP450 content in high does columbin group was significantly decreased to 0.68 fold that of model control group (P<0.01).â‘¡The catalytic activities of CYP1A1 (EROD), CYP1A2 (MROD), CYP2B1 (PROD), as well as the mRNA expression levels of CYP1A1, CYP1A2, CYP2B1 were raised in different degree. columbin showed significant inhibition effects on their activities and mRNA expression levels in experimental type 2 diabetic rats, which showed good dosage effect relationship.â‘¢columbin didn't significantly impact the activity and mRNA transcriptional level of CYP2D1 (DXM O-demethylase) in type 2 diabetes mellitus rats.â‘£The catalytic activities and mRNA levels of CYP2B1 (PROD), CYP2C11 (TOL-hydroxylase), and CYP2E1 (ANH) in model control group were decrease compared to normal control group.columbin raised the catalytic activities of these CYP450s, What is more, it positively modulated the mRNA transcriptional levels of them as well as their protein expression levels. Conclusion:The catalytic activities as well as the protein and mRNA expression of CYP450 isozymes were significantly augmented in type 2 diabetes mellitus rats, columbin reversed these changes through the regulation at transcriptional level, which make the drug metabolism in liver drug metabolism tend to be normal. |
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