The low dose combination of fenofibrate and rosiglitazone halts the progression of diabetes-induced experimental nephropathy

Abstract

The present study investigated the combined effect of low doses of fenofibrate (PPAR-alpha agonist) and rosiglitazone (PPAR-gamma agonist) in diabetes-induced experimental nephropathy. Rats were administered streptozotocin (55 mg/kg i.p., once) to induce experimental diabetes mellitus. The development of diabetic nephropathy was assessed biochemically and histologically. In addition, the lipid profile and renal oxidative stress were assessed. The single administration of streptozotocin produced diabetes, which induced the renal oxidative stress, altered the lipid profile, and subsequently produced nephropathy in 8 weeks by elevating serum creatinine, blood urea nitrogen, proteinuria, and inducing glomerular damage. Treatment with low dose fenofibrate (30 mg/kg/day p.o.) normalizes the altered lipid profile in diabetic rats, whereas the low dose rosiglitazone (1mg/kg/day p.o.) treatment has no effect on lipid alteration in diabetic rats. Treatment with low dose rosiglitazone partially reduced the elevated glucose level in diabetic rats, whereas fenofibrate treatment has no effect on it. The low dose combination of fenofibrate and rosiglitazone was more effective in attenuating the diabetes-induced nephropathy and renal oxidative stress as compared to treatment with either drug alone or lisinopril (1mg/kg/day p.o., employed as a standard agent). It may be concluded that diabetes-induced oxidative stress and lipid alterations may be responsible for the induction of nephropathy in diabetic rats. The concurrent administration of fenofibrate and rosiglitazone at low doses may have prevented the development of diabetes-induced nephropathy by reducing the lipid alteration, decreasing the renal oxidative stress and certainly providing the direct nephroprotective action.