The effect of indobufen on the activities of selected rat liver phase I and phase II drug metabolizing enzymes, peroxisomal beta-oxidation and hepatic glutathione status
Thomas, H.; Strolin Benedetti, M.; Dostert, P.; Oesch, F.
Journal of Pharmacy and Pharmacology 46(10): 833-837
1994
ISSN/ISBN: 0022-3573 PMID: 7699572 Document Number: 430734
Oral administration of indobufen to male rats for three days at daily doses of 5, 10 and 20 mg kg-1 resulted in no changes in liver total glutathione, cytosolic glutathione S-transferases or microsomal epoxide hydrolase. Reduced glutathione appeared slightly diminished to about 84% of control at the highest dose level. Microsomal cytochrome P450-dependent ethoxyresorufin O-de-ethylase and pentoxy-resorufin de-alkylase activities were decreased to 64% (not significantly) and 67% of control at the lowest dose level. 6-alpha- and 7-alpha-Hydroxytestosterone activities were decreased to 67 and 68% of control at the highest dose level. Cyanide-insensitive peroxisomal fatty acid beta-oxidation was increased to 223, 261 and 232% of control at doses of 5, 10, and 20 mg kg-1, respectively. The results obtained in this study are indicative of the action of indobufen as a weak peroxisome proliferator in male rat liver, and suggest a slight but toxicologically insignificant inhibitory action of this drug on microsomal cytochrome P450-dependent enzyme activities.