Decreased Phosphatidate Phosphohydrolase Activity in the Liver of Rats Exposed to Nicotinic Acid, Clofibrate and Gemfibrozil



Haghighi B¹ ; Kashani Z¹
Source: Indian Journal of Pharmacology Published:1999

Abstract

Objective: To investigate whether nicotinic acid, gemfibrozil and clofibrate exert their hypolipidemic effect by changing the activity of hepatic phosphatide phosphohydrolase (PAP). Methods: Male Wistar rats were intraperitoneally treated with one of the following: nicotinic acid, clofibrate, gemfibrozil, corresponding vehicle. All animals were given corn oil (p.o.) 2 h before injection. They were sacrificed at different time intervals and PAP enzyme activity was measured in liver homogenate. Serum triacylglycerol and cholesterol levels were also estimated. Results: Nicotinic acid inhibited PAP activity 35% with simultaneous decrease in serum triacylglycerol (29%) and cholesterol (22%) concentrations. Clofibrate also inhibited PAP activity (31%) with parallel decline in the concentrations of triacylglycerol (26%) and cholesterol (19%). Similar patterns were observed in rats injected with gemfibrozil in which the fall in PAP activity, triacylglycerol and cholesterol concentrations were 17%, 43% and 12% respectively. Conclusion: Hypolipemic effects of these compounds are, at least in part, resulted from inhibition of hepatic PAP activity, a key enzyme in the lipid metabolism.