Effect of HMG-CoA competetors on gene expression of eNOS and some biochemical changes in fructose fed rats

ABSTRACT

Syndrome X, also termed the metabolic syndrome, is a cluster of physiologic and metabolic abnormalities including hyperglycemia, hyperinsulinemia, hypertension and hyperlipidemia, the aim of the present study was to investigate the effect of HMG- CoA competetors [statins, simvastatin, and fluvastatin] on the gene expression of eNOS and Lipid profile in Fructose enriched diet [FED] rat model. The research was done on 40 male Sprague-Dawley rats. The rats were divided into the following 4 groups Group I [control group n=10] was allocated to normal rat chow diet with water alone, Group II [F-fed group n=10] was fed with fructose enriched chow for 4 weeks, Group III [Simvastatin treated F-fed group n=10], was fed with fructose enriched chow for 4 weeks followed by administration of simvastatin for a period of 2 weeks, Group IV [Fluvastatin treated F-fed group n=10], was fed with fructose enriched chow for 4 weeks followed by administration of fluvastatm for a period of 2 weeks. Fasting glucose, cholesterol, triglycerides, insulin, nitric oxide and gene expression of eNOS in the aorta were measured. The following results were obtained In group II [rats fed with a fructose rich diet] There was a significant increase in the levels of cholesterol, triglycerides, glucose, and insulin in comparison to the control group, There was a significant drop in both the plasma nitric oxide levels and in the expression of the eNOS gene in the aorta in comparison to the control group. In group III [Simvastatin treated fructose fed rats] There was significant reduction in the levels of cholesterol and triglycerides in comparison to group II, there was also a significant reduction in the levels of glucose and insulin in comparison to group II, on the other hand, the plasma nitric oxide levels and the expression of the eNOS gene in aorta were significantly elevated in comparison to group II. In group IV [Fluvastatin treated fructose fed rats] There was significant reduction in the levels of cholesterol and triglycerides in comparison to group II, there was also a significant reduction in the levels of glucose and insulin in comparison to group II, on the other hand, the plasma nitric oxide levels and the expression of the eNOS gene in aorta were significantly elevated in comparison to group II, on comparing the findings of group III with those of group IV It was evident that Fluvastatin was more effective in the treatment of all the studied parameters of the metabolic syndrome, except for the reduction of cholesterol levels, in which Simvastatin was slightly more effective, conclusion: The fructose enriched diet rat model provides an ideal means for creating a stimulated syndrome X in animals. Syndrome X caused an elevation in the levels of cholesterol triglycerides, glucose, and insulin. Syndrome X caused a reduction in the level of nitric oxide and a fall in the gene expression of eNOS in the aorta. Fluvastatin and Simvastatin caused a drop in the levels of cholesterol, triglycerides, glucose, and insulin. Fluvastatin and Simvastatin caused in elevation in the level of nitric oxide and a rise in the gene expression of eNOS in the aorta. Statins posses Pleiotropic [Non-Lipid-related] effects and mechanisms of action. Fluvastatin is more effective than Simvastatin in the reversal of all the pathological changes associated with syndrome X except when it came to the reduction of cholesterol levels in which Simvastatin was only slightly more effective. Our recommendations for future research is that more studies should be performed on the effects of other types of statins on syndrome X. Other factors such as life style modification including diet and exercise in addition to metformin and insulin sensitizers should be included in order to improve the cardiovascular outcome in syndrome X. Amelioration of cholesterol level by the use of statins had improved synthesis of NO as indicated by increased gene expression of eNOS and lowering of arterial blood pressure