APIGENIN ATTENUATES DIABETIC NEPHROPATHY IN TYPE 1 DIABETIC RATS

Abstract

Objective: The present study was designed to evaluate the effect of apigenin on progression and development of diabetic nephropathy in diabetic rats. Design and method: Adult male albino Wistar rats were divided into 7 groups: control, diabetic control, apigenin treatment groups (5–20 mg/kg; p.o.), ramipril (2 mg/kg; p.o.) and apigenin per se (20 mg/kg) group. Except control and per se groups, type 1 diabetes in other groups were induced by a single injection of streptozotocin (55 mg/kg; i.p). After confirmation of diabetes (FBG>250 mg/dl), rats were randomly divided into different treatment groups and observed for period of 8 months. Results: After 8 months, STZ resulted in attenuation of renal function (increased BUN and serum creatinine), increased oxidative stress and inflammation (increased cytokines and NF-kappa B) in the diabetic rats. In addition, there was fibrosis (increased transforming growth factor, fibronectin and type IV collagen), apoptosis (increased bax, caspase-3 and decreased bcl-2) and activation of MAPK pathway in diabetic-control group. These results were further supported by histopathological examination, which revealed presence of inflammation, collagen deposition and glomerulosclerosis in renal tissue of diabetic rats. In contrast, pre-treatment with apigenin significantly ameliorated STZ-induced functional and pathological changes in diabetic rats. In addition, it attenuated fibrosis, inflammation and apoptosis and also prevented activation of MAPK pathway in diabetic rats. All these protective effects were comparable to the ramipril treated group. Conclusions: Apigenin ameliorated oxidative stress, inflammation, apoptosis and fibrosis in diabetic rats by attenuation of MAPK pathway and prevented diabetic complication in diabetic rats.