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



Haghighi B¹ ; Kharazizadeh M¹ ; Attar MA¹
Source: Iranian Journal of Pharmaceutical Research Published:2007

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. Copyright © 2007 by School of Pharmacy Shaheed Beheshti University of Medical Sciences and Health Services.