Trolox C ameliorates hepatic drug metabolizing dysfunction after ischemia/reperfusion.
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.
Eum
Hyun-Ae
HA
College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Changan-gu, Suwon, Kyunggi-do 440-746, Korea.
Lee
Sang-Ho
SH
Lee
Sun-Mee
SM
D000818:Animals; D002839:Chromans / Q000494:pharmacology* / Q000627:therapeutic use; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*
D002839:Chromans; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid