Increased Expressions of eNOS and iNOS Correlate with Apoptosis of Diabetic Nephropathy in Streptozotocin-induced Type 1 Diabetic Rats

The present study was designed to evaluate the effects of high level of nitric oxide (NO) production and oxidative stress (OS) on nephropathology and to identify whether NO and OS have any correlation with apoptosis seen in diabetic kidney, elucidating the underlying mechanism(s) involved in the development of nephropathology in streptozotocin (STZ)-induced diabetic rats. Expression levels of caspase 3, caspase 9, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), 8-hydroxy-2'-deoxyguanosine (8-OHdG), for the detection of oxidative damage to DNA, were examined in diabetic kidney tissues. Results of the study revealed that the levels of 8-OHdG (P<0.005), eNOS (P<0.005), iNOS (P<0.005), caspase 3 (P< 0.005) and caspase 9 (P< 0.005) were remarkably higher in diabetic kidney tissues than in controls. In addition, STZ-treated animals showed significant loss of body weight and renal enlargement. It was suggested that apoptosis, OS and increased NO levels are involved in the pathogenesis of diabetic nephropathy. The results also strongly suggested that STZ-induced apoptosis through activation of the intrinsic pathway and that might be most likely related to increased NO levels. Moreover, high NO production was not only mediated by eNOS but also by iNOS. Increased NO production may contribute to hyperfiltration and microalbuminuria in early diabetic nephropathy. Furthermore, expression of 8-OHdG might give an idea of the progress and may be essential as it has a diagnostic significance for this disease. In conclusion, we believe that eNOS and iNOS overexpressions induce diabetic nephropathy by mediating apoptosis in STZ-induced rats.