Involvement of Endothelial Nitric Oxide Synthase, Caveolin and Haemoxygenase in Development of Experimental Diabetic Nephropathy in Rats

Endothelin nitric oxide synthase plays a important role in diabetic nephropathy. Caveolae are the morphological distinct invaginations on the suface of the plasma membrane and are of 50-100nm in diameter. Caveolin decreases nitric oxide by increasing binding of eNOS with caveolin. Hemeoxygenase-1 (OH1) is a enzyme involve in the catabolism of heme and leads to the formation of NO. Hemeoxygenase level was found to be decreased in diabetes. It has been documented that OH-1 decreases the interaction of eNOS with caveolin by increasing the availibilty of NO. This study was designed to determine the role of caveolin & haemoxygenase in eNOS-mediated NO synthesis & and release in DN. Diabetic nephropathy was induced by administering single dose of streptozotocin in wistar rats. DN was clinically assessed by estimation of various biochemical parameters and histopathological studies of renal tissue. DN was assessed by measuring serum creatinine, blood urea nitrogen, proteinuria, lipid profile, serum nitrite/nitrate ratio. The combination of daidzein(caveolin inhibitor) and Hemin (Hemoxygenase activator) showed significant improvement in (BUN, serum creatinine, proteinuria, urinary output, serum nitrite/ nitrate level) renal parameters studied for DN in comparison with single drug administration. Moreover, NG-nitro-Larginine methyl ester (L-NAME), a selective eNOS inhibitor abolished the ameliorative effect of combination of daidzein and hemin in DN in rats. The finding of this study suggest that haemoxygenase and caveolin plays a important role in the development of DN.