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Trolox C ameliorates hepatic drug metabolizing dysfunction after ischemia/reperfusion.

Abstract
The present study was done to determine the effect of trolox C, a hydrophilic analogue of vitamin E, on hepatic injury, especially the alteration in cytochrome P-450 (CYP)-dependent drug metabolism during ischemia and reperfusion (I/R). Rats were subjected to 60 min of hepatic ischemia and 5 h of reperfusion. Rats were treated intravenously with trolox C (2.5 mg/kg) or vehide (PBS, pH 7.4), 5 min before reperfusion. Serum alanine aminotransferase and lipid peroxidation levels were markedly increased after I/R. This increase was significantly suppressed by trolox C. Cytochrome P-450 content was decreased after I/R but was restored by trolox C. There were no significant differences in ethoxyresorufin O-dealkylase (CYP 1A1) and methoxyresorufin O-dealkylase (CYP 1A2) activities among any of the experimental groups. Pentoxyresorufin O-dealkylase (CYP 2B1) activity was decreased and aniline p-hydroxylase (CYP 2E1) activity was increased after I/R. Both these changes were prevented by trolox C. Our findings suggest that trolox C reduces hepatocellular damage as indicated by abnormalities in microsomal drug-metabolizing function during I/R, and that this protection is, in part, caused by decreased lipid peroxidation.
AuthorsHyun-Ae Eum, Sang-Ho Lee, Sun-Mee Lee
JournalArchives of pharmacal research (Arch Pharm Res) Vol. 25 Issue 6 Pg. 940-5 (Dec 2002) ISSN: 0253-6269 [Print] Korea (South)
PMID12510851 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Chromans
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid
Topics
  • Animals
  • Chromans (pharmacology, therapeutic use)
  • Cytochrome P-450 CYP1A1 (metabolism)
  • Cytochrome P-450 CYP1A2 (metabolism)
  • Ischemia (drug therapy, enzymology, metabolism)
  • Lipid Peroxidation (drug effects)
  • Liver (blood supply, drug effects, enzymology, metabolism)
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury (drug therapy, enzymology, metabolism)

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