Potential renoprotective effects of Ramipril and vitamin E in streptozotocin - induced diabetic male albino rats

ABSTRACT

Hyperglycemia, a well recognized pathogenic factor of long-term complications in diabetes mellitus, not only generates more reactive oxygen species but also attenuates antioxidative mechanisms. Therefore, oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy. Tumor necrosis factor-alpha [TNF-alpha] has been implicated as a link between insulin resistance, diabetes and endothelial dysfunction. The present study was undertaken to investigate whether treatment of streptozotocin-induced diabetic rats with a combination therapy of angiotensin converting enzyme inhibitor [ramipril] and vitamin E reduce the possible hazards of oxidative damage induced by reactive oxygen species. Forty male adult albino rats divided into 5 groups each included 8 rats and arranged as control group, streptozotocin-induced diabetic group [60 mg/kg b.wt.i.p.], ramipril + diabetic group, vitamin E + diabetic group and ramipril + vitamin E + diabetic group. Ramipril was given in a dose of 10 vitamin E in a dose of 100 mg/kg/day orally for 15 days. The results of the present study showed that diabetes produced nephrotoxicity established by significant increase in urinary proteins and serum creatinine and significant decrease in creatinine clearance. In addition there was a significant decrease in nitric oxide [NO] and antioxidant enzymes superoxide dismutase [SOD], glutathione peroxidase [GPx]. On the other hand an important observations that lipid peroxides and 8-hydroxydeoxyguanosine [8-OHdG] indices of oxidative tissue injury were significantly increased in kidneys of diabetic rats as well as significant increase in serum TNF-alpha. Treatment of diabetic rats with combination therapy of ramipril + vitamin E produced amelioration of nephrotoxicity induced by induction of diabetes where urinary proteins, serum creatinine,malondiapdehyde [MDA],TNF-alpha and 8-OHdG were significantly reduced while nitric oxide [NO] as well as creatinine clearance, SOD and GPx were significantly increased. Moreover there was an improvement in glucose level. These biochemical data were confirmed by the changes observed by histopathological examination of the kidney. Finally, the biochemical improvement following combination therapy in streptozotocin-induced diabetic rats was more evident than histopathological one, thus the use of ramipril and vitamin E in the treatment of diabetes mellitus may have a renoprotective effect