Role of adenylyl cyclase activator in controlling experimental diabetic nephropathy in rats.

The present study aimed to investigate the role of adenylyl cyclase activator in preventing diabetic nephropathy in rats. Renal function parameters, renal hypertrophy, lipid profile, markers of oxidative stress and free radical scavenging activities were assessed. Histopathology was performed to confirm Streptozotocin induced renal morphological changes in diabetic rats. Male Wistar rats were used in the present study to reduce the effect of estrogen. Rats were subjected to high fat diet (HFD) for two weeks followed by low dose of Streptozotocin (STZ) [35 mg/kg, i.p.] to develop experimental diabetic nephropathy in eight weeks. Two weeks treatment with low dose of Forskolin (10 mg/kg) reduced the level of diabetic nephropathy markers but results observed were not significant. Whereas, Forskolin intermediate dose (20 mg/kg) and high dose (30 mg/kg) treated rats significantly attenuated diabetes induced elevated renal function parameters and endogenous antioxidants enzymatic activities. High dose of Forskolin was found to be more effective in attenuating the renal structural and functional abnormalities. Forskolin prevented renal structural and functional abnormalities in diabetic rats. Histopathological evaluation revealed that Forskolin (20 mg/kg and 30 mg/kg) treated diabetic rats demonstrated reduced vacuolar degeneration of tubules and glomerulosclerosis. In the present study, Glibenclamide (0.6 mg/kg) and Atorvastatin (0.5 mg/kg) were used as standard drugs. Our results demonstrated synergistic effects, when high dose of Forskolin was co-administered with standard drugs. In conclusion, treatment with adenylyl cyclase activator, Forskolin in diabetic rats reduced the elevated serum glucose level, biomarkers of renal morphological dysfunction, renal hypertrophy, dyslipidaemia, oxidative stress and improved renal structure, function and enhanced level of endogenous antioxidants. Forskolin has a potential to prevent nephropathy without showing any effect on body weight in diabetic rats.