Abstract
We have previously shown that the low-dose combination of fenofibrate and rosiglitazone might halt the progression of diabetes-induced nephropathy in rats. The present study investigated the combined effect of fenofibrate (PPAR alpha agonist) and telmisartan (AT(1) receptor antagonist) in diabetes-induced onset of nephropathy in rats. The single administration of streptozotocin (STZ, 55 mg/kg i.p.) produced diabetes mellitus, which subsequently produced nephropathy in 8 weeks by markedly elevating serum creatinine, blood urea nitrogen and microproteinuria. In addition, histopathological studies revealed the development of renal structural abnormalities such as mesangial expansion, glomerular and tubular damage. Moreover, diabetes-induced nephropathy was accompanied with high renal oxidative stress and lipid alteration. Treatment with fenofibrate (80 mg/kg/day, p.o., 4 weeks) and telmisartan (10 mg/kg/day, p.o., 4 weeks) either alone or in combination did not affect the elevated glucose levels in diabetic rats. Albeit treatment with fenofibrate normalizes the altered lipid profile in diabetic rats, telmisartan treatment has no effect on it. Treatment with fenofibrate and telmisartan either alone or in combination markedly prevented diabetes-induced onset of nephropathy and renal oxidative stress. Their combination was as good as to their individual treatment, but not superior in attenuating the diabetes-induced nephropathy and renal oxidative stress. It may be concluded that diabetes-induced oxidative stress and lipid alteration, besides hyperglycemia, could play a key role in the induction of nephropathy. Fenofibrate and telmisartan individual treatment was equipotent in preventing the onset of diabetes-induced experimental nephropathy, while their combination did not afford additional benefits in preventing the disease induction of the diabetic kidney. (C) 2012 Elsevier Ltd. All rights reserved.