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

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 epoxid e 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-alkyl ase activities were decreased to 64% (not significantly) and 67% of co ntrol at the lowest dose level. 6 alpha- and 7 alpha-Hydroxytestostero ne activities were decreased to 67 and 68% of control at the highest d ose level. Cyanide-insensitive peroxisomal fatty acid beta-oxidation w as 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 indic ative 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-dependen t enzyme activities.