The present study has been designed to investigate the combined effect of daidzein (caveolin inhibitor) and hemin (hemoxygenase activator) in diabetic nephropathy in wistar rats. Diabetes mellitus in rat was induced by feeding of high-fat diet (HFD) for 2 weeks, followed by single dose of streptozotocin (STZ) (35 mg/kg, i.p.) further followed by HFD for further 8 weeks. DN was clinically assessed by estimation of various biochemical parameters and histopathological studies of renal tissue. DN was assessed by measuring serum creatinine, renal cortical collagen content, serum nitrite/nitrate ratio, renal TBARS, reduced glutathione levels. The combination of daidzein and hemin showed significant improvement in ( serum creatinine, kidney weight/ body weight, renal cortical collagen content, nitrite/ nitrate level, renal TBARS, reduced glutathione) renal parameters studied for DN in comparison with single drug administration. L-NAME (NG-nitro-L-arginine methyl ester) a selective eNOS inhibitor abolished the ameliorative effect of combination of daidzein and hemin in DN in rats. It may be concluded that Daidzein in combination with hemin may enhance the level of renal nitric oxide by decreasing the expression of caveolin. . Treatment with daidzein with hemin was more effective as compared to individual drugs. These finding provide mechanistic insights to explain renoprotective effect of this combined therapy in diabetes.
