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 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.
Thomas
H
H
Institute of Toxicology, University of Mainz, Germany.
Strolin Benedetti
M
M
Dostert
P
P
Oesch
F
F
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004851:Epoxide Hydrolases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D054833:Isoindoles; D008099:Liver / Q000201:enzymology*; D008297:Male; D008830:Microbodies / Q000378:metabolism*; D010084:Oxidation-Reduction; D010654:Phenylbutyrates / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D005227:Fatty Acids; D054833:Isoindoles; D010654:Phenylbutyrates; C020371:indobufen; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D005978:Glutathione