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.