Role of the Cytochrome P450 2A5 in Bilirubin Metabolism and Clearance in C57BL/6 Mice.

Abstract

Cytochrome P450 2A5 (CYP2A5) is uniquely induced in response to liver injury, indicating that CYP2A5 may have a cytoprotective function. Others have proposed that CYP2A5 protects hepatocytes by oxidizing bilirubin to biliverdin in a redox-cycle to prevent toxic bilirubin accumulation. We hypothesize that CYP2A5 enhances bilirubin clearance by excreting polar dipyrroles when UDP-glucoronosyltransferase 1A1 conjugating capacity is impaired by liver injury. The objective of this study is to compare hepatic bilirubin metabolism and clearance in wild type and Cyp2a5-null C57BL/6 mice. Microsomal bilirubin disappearance and biliverdin production in vitro were quantified by HPLC with UV-Vis detection. Bilirubin clearance was assessed by measuring serum levels one hour after bilirubin injection. Our results indicate that bilirubin metabolism and clearance are not influenced by CYP2A5. We conclude that the role of CYP2A5 in hepatoprotection does not involve bilirubin redox-cycling and elimination in C57BL/6 mice.