الفهرس 
Diabetes Mellitus and Oxidative StressOnly 14 pages are availabe for public view
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Abstract
Simvastatin is 3-hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which is prescribed extensively for cholesterol lowering agent. Recent compelling evidence suggests that statins have the beneficial pleiotropic effects. They are directly involved in restoring or improving endothelial function, attenuating vascular remodeling, inhibiting vascular inflammatory response, and perhaps, stabilizing atherosclerotic plaques.
Ezetimibe specifically blocks the absorption of cholesterol for the intestine and other related phytosterols.
The aim of this study was to investigate the effects of simvastatin or ezetimibe either as a monotherapy or in combination on metabolic, endothelial and renal dysfunction associated with streptozotocin- induced diabetes in wister rats. Additionally, the possible role of superoxide dismutase was investigated.
Wister albino rats were injected by a single intraperitoneal injection of small dose of streptozotocin (STZ) for induction of model of diabetes. Half of each group (n=6/group) was examined for measuring systolic blood pressure and sacrificed after 6 weeks for measuring the effect of drugs on lipid profile, vascular function and superoxide dismutase activity in serum and aortic tissue. The other half (n=6/group) was sacrificed at the end of 12th week for measuring renal functional changes (serum creatinine, superoxide dismutase enzyme activity in renal glomeruli and histopathological changes in renal glomeruli).
Induction of diabetes mellitus was associated with vascular, metabolic and renal dysfunctions which was associated with significant reduction in serum and tissues (aorta and renal) SOD activity.
Chronic treatment with simvastatin (2mg/kg/day) or ezetimibe (5mg/kg/day) as a monotherapy was found to be effective in ameliorating lipid profile, level of serum, aortic and renal SOD activity and serum creatinine with reduction of the systolic blood pressure. To some extend, ezetimibe treatment improved endothelium-dependant relaxation but it was found to be less effective as regard norepinephrine induced contraction of the isolated aortic and renal corpuscle injury.
Addition of ezetimibe to simvastatin enhanced or potentiated the ameliorative effect of simvastatin on vascular, metabolic and renal dysfunctions associated with STZ-induced diabetes in wistar rats.
In conclusion, these findings underscore the importance of ezetimibe to be added to simvastatin to ameliorate vascular, metabolic and renal dyfunctions.
Key words: Simvastatin, ezetimibe, superoside dismutase, norepinephrine,
blood pressure, aortoic ring, renal functions.