Influence of sodium monoketocholate on the hypolipidemic activity of lovastatin in healthy and diabetic rats

Abstract

Recent findings regarding the physiological transport mechanisms and metabolism of bile acids have led to an increased interest in their synthetic derivatives, especially as transmucous transporters. The aim of this study was to examine the influence of the synthetic sodium salt of monoketocholic acid (Na-MKHA) on the hypolipidemic activity of lovastatin. The effects of a 7 days administration of lovastatin (20 mg/kg b.w.) (experimental group 1, n=5) and a combination of lovastatin (20 mg/kg b.w.) and Na-MKHA (2 mg/kg b.w.) (experimental group 2, n=5) in group of healthy and diabetic male Wistar rats were investigated. The animals in the control group of healthy (n=5) and diabetic (n=5) rats were treated with physiological saline (10 ml/kg b.w.) per os twice a day. In the healthy rats, lovastatin increased the low density lipoprotein (LDL) (32.14%) and non-high density lipoprotein (HDL) (15.38%) cholesterol and decreased HDL cholesterol levels (9.89%), and also increased the investigated atherogenic ratios. Na-MKHA significantly potentiated lovastatin activity, and its effects on the LDL (p<0.05; 102.70%), HDL (p<0.01; 32.93%) and non-HDL (p<0.05; 65%) cholesterol levels, as well as the LDL/HDL (p<0.02; 231.11%), total cholesterol/HDL (p<0.02; 70.52%) and non-HDU/HDL cholesterol ratios (p<0.02; 167.12%). In diabetic animals, the potentiating effect of Na-MKHA was not significant. The stimulatory effect of Na-MKHA is probably a consequence of the intensified transmembrane transport of lovastatin due to the direct action of bile acids on the cell membranes, as well as a result of their enhanced transport via specific bile acid transport systems.