Clinical Pharmacology & Biopharmaceutics
Open Access

Abstract

Background: Diabetes is recognized as a major risk factor in the development of cerebrovascular disease along with other factors as hypertension, dyslipidemia and obesity. Stroke occurs 2 to 4 times more frequently in adults with diabetes than in those who are healthy. Statins represent promising classes of agents for prevention or treatment of stroke. Materials & Methods: The rats were divided into five groups of ten rats each. (I) Normal control group; (II) Diabetic rats (diabetes was induced by a single intraperitoneal injection of streptozotocin 55 mg/kg, in citrate buffer, pH 4.5); (III) Ischemia/reperfusion diabetic group were subjected to cerebral ischemia (I) for 1 hr/24 h reperfusion (R), and (IV) and (V) groups were treated with simvastatin (20 mg/kg), and fluvastatin (10 mg/kg) for 10 days, respectively before undergoing ischemia/reperfusion. Results: Diabetic and diabetic cerebral ischemic-reperfused rats showed significant reduction in body weight, hyperglycemia, increased glycated hemoglobin %, and a change in lipid profile characterized by elevated serum cholesterol, LDL, triglycerides levels and increased atherogenic indices while serum HDL remains unchanged. These groups showed increased formation of lipid peroxides (MDA) and depletion of internal antioxidant GSH in brain tissues. I/R injury increased infarction areas, serum NO level, and inflammatory marker; serum ICAM-1 levels and up-regulated brain iNOS expression in diabetic animals. Moreover, increased brain expressions of apoptotic P53 and antiapoptotic Bcl-2 proteins were noted. Finally, I/R injury was confirmed by brain histopathological changes. Statins treatment was not able to change blood glucose level or lipid profile, but they provided protection against cerebral I/R injury as indicated by reduced oxidative stress, decline in inflammatory markers and infarction areas. Statins reduced ICAM-1 and induced down regulations of p53 and Bcl-2 and iNOS expression. The results of this research suggest that enhanced cerebral apoptosis is critically involved in cerebral damage associated with diabetes and cerebral ischemic-reperfusion. These results suggested that statins may represent a new approach for treating cerebrovascular diseases. Further clinical evidence is needed to support these observations.

Biography

Email: hananhhagar@yahoo.com