Possible Involvement of Hepatic Phosphatidate Phosphohydrolase in the Mechanisms of Actions of Certain Antilipemic Drugs in Rats

Abstract

The effects of therapeutic doses of dillsun, garsin, antum and statins on rat liver cytosolic phosphatidate phosphohydrolase (PAP) activity, a key enzyme in triacylglycerol synthesis, and on serum and liver lipids were examined. Lovastatin and simvastatin both stimulated the enzyme activity by 29% and 43%, respectively. The stimulatory effects were dose-dependent and accompanied by the decline in triacylglycerol and cholesterol concentrations of serum (20-29%) and liver (12-29%) suggesting a possible feed-back mechanism for PAP control. Dillsun (0.5-2 ml/day) did not affect PAP activity and liver lipids but lowered serum triacylglycerol (27%) and cholesterol (20%) concentrations at a dose of 2 ml/day. Antum administration also showed similar pattern as dillsun except that it caused a decrease in the liver lipids as well. Garsin (250-1000 mg/Kg) inhibited PAP activity (14-22%) with simultanous decrease in the liver and serum lipids; maximum decrease in serum triacylglycerol and cholesterol were 14% and 21%, respectively. The data demonstrated that the antilipidemic drugs tested exert their effects, at least in part, through alteration of hepatic PAP activity.