Trigonelline ameliorates diabetic hypertensive nephropathy by suppression of oxidative stress in kidney and reduction in renal cell apoptosis and fibrosis in streptozotocin induced neonatal diabetic (nSTZ) rats

Oxidative stress and apoptotic cell death in kidney have been suggested as contributing factors in the development and complication of diabetes especially in diabetic nephropathy (ON). This study investigated the effects of trigonelline (TG) on the renal functional, morphological changes and renal apoptosis in neonatal diabetic rats, a model of non-insulin-dependent diabetes mellitus. Diabetes mellitus was induced in one day old neonatal Wistar rat pups by an intraperitoneal (i.p.) injection of streptozotocin (STZ) (50 mg/kg) and monitored for 16 weeks thereafter. The diabetic rats were divided as follows: the nSTZ diabetic group, the TG (50 mg/kg) treated diabetic group, and the TG (100 mg/kg) treated diabetic group. The age matched nondiabetic group received an injection of citrate buffer (0.1 M, pH 4.5). At the end kidney samples were taken for light microscopic examinations. The levels of serum creatinine and BUN were significantly low in TG (100 mg/kg) treated diabetic rats. Glomerular filtration rate was improved in TG treated rats. The activities of antioxidant enzyme and membrane bound enzyme were decreased and the levels of tumor necrotic factor (TNF-alpha) and hydroxyproline content were increased in renal tissues of the diabetic group. TG (100 mg/kg/day) treatment for a period of 4 weeks showed significant ameliorative effects on all the biochemical parameters studied. Biochemical findings were supported by histological studies. The degenerative changes in kidney tissue and fibrosis were alleviated in the TG treated groups. These results suggested that TG might have a significant role in alleviating kidney damage in nSTZ-diabetic rats. (C) 2012 Elsevier B.V. All rights reserved.