Effect of the tranquilizer mebicar on lipid metabolism and lipid peroxidation on the model of hypokinesia in rats

Abstract

Daffy 18-hour hypokinesia induces atherogenic shifts in the blood lipid spectrum and activates lipid peroxidation in rats. Mebicar is shown to have a correcting effect on lipid metabolism and on the intensity of lipid peroxidation. Key Words: hypokinesia; lipid metabolism; lipid peroxidationStress is known to play a crucial role in the pathogenesis of atherosclerosis [3,8,9], and therefore it makes sense to seek new antiatherosclerotic and hypolipidemic drugs among the tranquilizers [3,10,11]. Our attention was drawn to the Russian-manufactured mild tranquilizer mebicar, a member of the bieyclic bisurea family, whose effect on lipid metabolism has been demonstrated in clinical studies [5]. In the present study we evaluated the effect of mebicar on the blood lipid spectrum and intensity of lipid peroxidation (LPO) in rats under conditions of hypokinesia. This model was chosen as a high-risk state for atherosclerosis development [ 1,2,6]. MATERIALS AND METHODSThe experiment was carried out on 75 nonpedigree male albino rats with an initial weight of 180-200 g. The animals were fed standard vivarium chow. For hypokinesia modeling the animals were placed in special closely fitting Plexiglas boxes with free access to food and water for 18 hours each day. During the remaining 6 hours the animals were free and the boxes were cleaned. In the first experimental series, performed so as to develop the method, the animals (n=30) were divided into 2 groups: 15 intact rats (group 1) and 15 in a state of hypokinesia (group 2). In series II the rats (n=45) were divided into 3 groups of 15: intact controls (group 1) and animals in a state of hypokinesia receiving intragastmLly either twice-distilled water or mebicar (250 mg/kg) (groups 2 and 3, respectively).On days 7 and 14 of the experiment the animals were weighed, and blood was collected. The total cholesterol (TCH), high density lipoprotein cholesterol (HDL-CH), and triglycerides were measured with diagnostic kits using a Labsystems autoanalyzer. The concentration of phospholipids was determined by the content of lipid phosphorus in a lipid-protein precipitate [7]. LPO intensity was assessed by the blood content of the end LPO product, malonic dialdehyde (MDA), measured in the reaction with 2-thiobarbituric acid [4]. On day 14 the animals were sacrificed and the relative weight of the adrenals was determined.The exparimental data were processed statistically using the Student t test. RESULTSIn series I the animals in a state of hypokinesia lost 6.3% (p<0.005) and 14.6% (p<0.001) of their body