Kojic-Damjanov Suncica, Djeric Mirjana, Mikov Momir, Kuhajda Ksenija, Kevresan Slavko
Institute of Laboratory Medicine, Clinical Center of Voivodina, Novi Sad, Republic of Serbia.
Eur J Drug Metab Pharmacokinet. 2008 Apr-Jun;33(2):77-84. doi: 10.1007/BF03191024.
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.
近期有关胆汁酸生理转运机制和代谢的研究发现，引发了人们对其合成衍生物的更多关注，尤其是作为透黏膜转运体的衍生物。本研究旨在探讨单酮胆酸合成钠盐（Na-MKHA）对洛伐他汀降血脂活性的影响。研究了在健康和糖尿病雄性Wistar大鼠组中，连续7天给予洛伐他汀（20mg/kg体重）（实验组1，n = 5）以及洛伐他汀（20mg/kg体重）与Na-MKHA（2mg/kg体重）联合用药（实验组2，n = 5）的效果。健康（n = 5）和糖尿病（n = 5）大鼠对照组的动物每天经口给予生理盐水（10ml/kg体重）两次。在健康大鼠中，洛伐他汀使低密度脂蛋白（LDL）胆固醇升高（32.14%）、非高密度脂蛋白（HDL）胆固醇升高（15.38%），高密度脂蛋白胆固醇水平降低（9.89%），并且还使所研究的致动脉粥样化比率升高。Na-MKHA显著增强了洛伐他汀的活性，其对LDL（p<0.05；102.70%）、HDL（p<0.01；32.93%）和非HDL（p<0.05；65%）胆固醇水平，以及LDL/HDL（p<0.02；231.11%）、总胆固醇/HDL（p<0.02；70.52%）和非HDU/HDL胆固醇比率（p<0.02；167.12%）均有影响。在糖尿病动物中，Na-MKHA的增强作用不显著。Na-MKHA的刺激作用可能是由于胆汁酸对细胞膜的直接作用导致洛伐他汀跨膜转运增强，以及通过特定胆汁酸转运系统其转运增强的结果。
