Effects of some anti-inflammatory drugs on biochemical values and on hepatic peroxisomal enzymes of rat.

Abstract

Effects of tolmetin, diclofenac Na, fenbufen, alclofenac, aminopyrine, mepirizole, thiaramide and aspirin as a positive control, which are widely used in this country as anti-inflammatory drugs, and on body and liver weights, triglyceride and cholesterol level and hepatic peroxisomal enzymes of normolipemic rats were examined. All of these drugs except diclofenac Na affected the enzyme composition of hepatic peroxisomes. Tolmetin (100 mg/kg) and fenbufen (50 mg/kg) increased carnitine acetyltransferase (CAT) and fatty acyl-coenzyme A oxidizing system (FAOS) activities, which participate in hepatic lipid metabolism. The latter also increased the activity of D-amino acid oxidase slightly. Alclofenac (300 mg/kg) increased the activities of FAOS, CAT and carnitine palmitoyltransferase which has been known as the rate-limiting enzyme of fatty acid oxidation in mitochondria, and decreased those of catalase and urate oxidase. Aminopyrine (300 mg/kg) increased the activities of catalase and FAOS. However, none of the above drugs influenced liver weight, serum or liver lipid levels. Mepirizole (300 mg/kg) increased the activities of FAOS and CAT about 2-fold, whereas the activities of catalase and urate oxidase and serum triglyceride level were decreased. Furthermore, these drugs showed no enhancement of the biosynthesis of peroxisome proliferation associated polypeptide having a molecular weight of 80000. From these results, it is concluded that although these drugs have an influence on the enzyme composition of hepatic peroxisomes, they may not induce the peroxisome population in hepatic cells. Thus, the possibility of hepatocarinogenicity and lipid lowering effect through the peroxisome-proliferation would be excluded.