The present study has been designed to investigate the combined effect of daidzein (caveolin inhibitor), hemin
(hemoxygenase activator) and BMS182874 (endothelin receptor antagonist) in diabetic nephropathy in wistar rats.
Diabetic nephropathy was induced by administering single dose of streptozotocin in wistar rats. DN was clinically
assessed by the estimation of various biochemical parameters and histopathological studies of renal tissue. DN was
assessed by measuring serum creatinine, blood urea nitrogen, proteinuria, renal cortical collagen content, lipid profile,
serum nitrite/nitrate ratio, renal TBARS and reduced glutathione levels. The combination of daidzein, hemin and
BMS182874 showed significant improvement in (BUN, serum creatinine, proteinuria, urinary output, 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 as well as a combination of two drugs. L-NAME (NG-nitro-
L-arginine methyl ester) a selective eNOS inhibitor abolished the ameliorative effect of combination of daidzein, hemin
and BMS182874 in DN in rats. It may therefore be concluded that Daidzein in combination with hemin may enhance the
level of renal nitric oxide by decreasing the expression of caveolin. BMS182874 shows renoprotection by inhibiting
RAAS system and through reactivation of NO synthesis. These findings may provide mechanistic insights to explain
renoprotective effect of this combined therapy in diabetes.