Effects of spironolactone, losartan and combination therapy on diabetic nephropathy in OLETF rats

Abstract

[한글]

[영문]

Backgrounds Although there were some evidences that spironolactone could attenuate albuminuria in type 2 diabetes via anti-inflammatory and anti-oxidants effects, the effects of spironolactone on VEGF expression on kidney in diabetic nephropathy were not elucidated. In this study, we examined the effects of spironolactone, losartan, and combination with spironolactone and losartan on albuminuria and glomerular VEGF expression in type 2 diabetic rat model. Methods Thirty-three OLETF rats were divided into the following four groups and treated with different medications from 25 weeks to 50 weeks: control OLETF group for diabetic controls (N=5), spironolactone group (N=10), losartan group (N=9), and combination group (N=9). At 15, 30, and 50 weeks, urine was collected for 24 hours urine protein amounts and albumin-creatinine-ratio (ACR). At 50 weeks, all experimental rats were sacrificed and both kidneys were prepared for western blot and RT-PCR for VEGF, TGF-β, and type IV collagen.Results At 50 weeks, ACR was significantly decreased in losartan and combination regimen treated group (1.21±0.81, 1.01±0.99, p<0.05) compared with that of control OLETF group (4.35±1.19). But, in spironolactone treated group, ACR was not decreased. There was a significant reduction in glomerular VEGF mRNA levels in spironolactone and combination regimen treated group compared with control OLETF group. But, western blot did not show significant difference among groups. TGF-β and type IV collagen expressions were significantly decreased in spironolactone and combination regimen treated groups. MDA levels were significantly decreased in combination regimen treated group than that of control diabetic rat group.Conclusion These results suggest that combination therapy of spironolactone and losartan may contribute the beneficial effect on diabetic nephropathy by reducing VEGF, TGF-β, type IV collagen expression and oxidative stress in type 2 diabetic rat models.