Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Diabetic nephropathy (DN) is becoming an ever larger health burden worldwide, more effective therapies are needed. In the present study, the antidiabetic and renoprotective effects of aliskiren a renin inhibitor and spironolactone an aldosterone antagonist were evaluated in streptozotocin (STZ) induced DN in rats. Diabetic nephropathy was induced by a single intraperitoneal injection of STZ (65 mg/kg). After 3 days, rats were divided into 6 groups: normal, diabetic, diabetic rats treated with gliclazide (10 mg/kg/day), diabetic rats treated with aliskiren (50 mg/kg/day), diabetic rats treated with spironolactone (20 mg/kg/day) and diabetic rats treated with combination of aliskiren (25 mg/kg/day) and spironolactone (10 mg/kg/day). After one month of treatment, mean arterial blood pressure and heart rate were recorded. Then rats were euthanized and serum was separated for determination of glucose, insulin, kidney function tests, superoxide dismutase activity (SOD), adiponectin and nitric oxide (NO). Kidneys were isolated, one kidney was used for estimation of malondialdehyde (MDA), reduced glutathione (GSH) and tumor necrosis factor alpha (TNF-Ü), whereas the other kidney was used for histopathological study and immunohistochemical measurement of caspase 3 and transforming growth factor beta (TGF-Ý). In addition, islets of Langerhans were isolated from non-fasting normal rats by collagenase digestion technique. Isolated Ý cells were divided into 11 groups and were treated as follows: normal control, 20 æl (40 omol/L) gliclazide, 20 æl (100 omol/L) aliskiren alone or in combination with gliclazide, 20æl (5æg/L) spironolactone alone or in combination with gliclazide

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