6533b858fe1ef96bd12b651c
RESEARCH PRODUCT
The Effect of Indobufen on the Activities of Selected Rat Liver Phase I and Phase II Drug Metabolizing Enzymes, Peroxisomal β-oxidation and Hepatic Glutathione Status
P DostertH ThomasH ThomasM Strolin BenedettiFranz Oeschsubject
Malemedicine.medical_specialtyPharmaceutical ScienceIsoindolesBiologyMicrobodieschemistry.chemical_compoundCytochrome P-450 Enzyme SystemOral administrationInternal medicinemedicineAnimalsGlutathione TransferaseEpoxide HydrolasesPharmacologychemistry.chemical_classificationIndobufenDose-Response Relationship DrugFatty AcidsFatty acidCytochrome P450Rats Inbred StrainsGlutathionePeroxisomeGlutathionePhenylbutyratesRatsEndocrinologyLiverchemistryMicrosomal epoxide hydrolaseMicrosomebiology.proteinOxidation-Reductionmedicine.drugdescription
Abstract 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 pentoxyresorufin de-alkylase activities were decreased to 64% (not significantly) and 67% of control at the lowest dose level. 6α- and 7α-Hydroxytestosterone activities were decreased to 67 and 68% of control at the highest dose level. Cyanide-insensitive peroxisomal fatty acid β-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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1994-10-01 | Journal of Pharmacy and Pharmacology |