Effects of Trolox on the activity and gene expression of cytochrome P450 in hepatic ischemia/reperfusion

Br J Pharmacol. 2004 May;142(1):35-42. doi: 10.1038/sj.bjp.0705758. Epub 2004 Mar 29.


1. The aim of this study was to investigate the effect of Trolox on hepatic microsomal cytochrome P450 (CYP) activity and gene expression during ischemia and reperfusion (I/R). 2. Rats were subjected to 60 min of hepatic ischemia, and 5 h (acute phase) and 24 h (subacute phase) of reperfusion. Rats were treated intravenously with Trolox (2.5 mg kg(-1)) or vehicle, 5 min before reperfusion. 3. The serum alanine aminotransferase level and lipid peroxidation were increased as a result of I/R. These increases were attenuated by Trolox. Reduced glutathione concentration decreased in I/R group, and this decrease was inhibited by Trolox. 4. Both total hepatic CYP content and NADPH-cytochrome P450 reductase activity decreased after I/R, which were restored by Trolox. 5. CYP1A1 activity and its protein level decreased 24 h after reperfusion; decreases which were prevented by Trolox. Both the activity and mRNA expression of CYP1A2 decreased 24 h after reperfusion. The decrease in CYP1A2 mRNA was prevented by Trolox. CYP2B1 activity and mRNA expression decreased 5 h after reperfusion. The decrease in CYP2B1 activity was prevented by Trolox. In contrast, the CYP2E1 activity and its protein level increased 5 h after reperfusion and this increase was prevented by Trolox. 6. The expression of TNF-alpha and iNOS mRNAs increased after I/R. Trolox inhibited increase in iNOS mRNA expression. 7. Trolox ameliorates hepatic drug-metabolizing dysfunction, as indicated by abnormalities in CYP isoforms during I/R, and this protection is likely due to the scavenging of reactive oxygen species.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromans / pharmacology*
  • Chromans / therapeutic use
  • Cytochrome P-450 Enzyme System / biosynthesis*
  • Cytochrome P-450 Enzyme System / genetics
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology
  • Liver / blood supply
  • Liver / drug effects*
  • Liver / enzymology*
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / enzymology*


  • Chromans
  • Cytochrome P-450 Enzyme System
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid