Effect of biliary obstruction and internal biliary drainage on hepatic cytochrome P450 isozymes in r

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AIM: To investigate the total cytochrome P450 (CYP)content, microsomal mixed-function oxidase (MFO)activity, and expression of mRNAs for various CYP isozymes in a simple rat model of reversible obstructive jaundice.METHODS: Obstructive jaundice was created in male rats by causing bile duct obstruction with polyester tape.In another group of rats, bile duct obstruction was followed by intal biliary drainage after releasing the tape.The expression of various CYP isozyme mRNAs was semi-quantitatively assessed by competitive RTPCR.RESULTS: The total CYP content and microsomal MFO activity showed a significant decrease after biliary obstruction, but reted to respective control levels after biliary drainage.A marked reduction in the expression of CYPIA2, 2B1/2, 2Cll, 2E1, 3A1, and 3A2 mRNA was detected during biliary obstruction,while expression increased significantly toward the control level after biliary drainage.Although expression of CYP4A1 mRNA showed no reduction during biliary obstruction, it still increased significantly after biliary drainage.CONCLUSION: These results suggest that not only obstructive jaundice, but also the subsequent intal biliary drainage may affect regulatory medications of the synthesis of individual CYP isozymes differently.
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