Preventive effects of betulinic acid on streptozotocin-nicotinamide induced diabetic nephropathy in male mouse

Abstract

Background: Diabetic nephropathy is defined as a progressive decline in glomerular filtration rate, accompanied by proteinuria. Betulinic acid (BA) employs in the treatment and management of diabetes. Objectives: This study was designed to evaluate the preventive effects of BA on streptozotocin-nicotinamide (STZ-NA) induced diabetic nephropathy in male mouse. Materials and Methods: In this experimental study, 60 adult male NMRI mice (20-25 g) were obtained. Type 2 diabetes induced by intraperitoneal (IP) injection of a single dose of STZ (65 mg/kg) 15 minutes after an IP administration of NA (120 mg/kg). Then, mice were divided into six groups; control, diabetes, diabetes + BA (10, 20 and 40 mg/kg), and diabetes + metformin (200 mg/kg). Twenty-four hours after the last drug administrations, plasma samples were obtained and maintained at −20°C for albumin, blood urea nitrogen (BUN) and creatinine (Cr) measurements. Renal tissue was removed, fixed in 10% formalin solution and stained with hematoxylin and eosin. Results: Plasma albumin level decreased in diabetic mice (P < 0.05) and increased in diabetic BA 10, 20, 40 mg/kg and metformin treated mice versus to diabetes group. BUN increased in diabetes (P < 0.001), and administration of BA 10, 20, 40 mg/kg and metformin showed a significant decrease in BUN of diabetic treated mice. Plasma Cr levels increased in diabetes (P < 0.01) but, BA 10, 20, 40 mg/kg and metformin decreased this enhancement of plasma Cr levels. Renal histopathology indicated normal appearances reduced in diabetic mice and BA or metformin administration improved them. Conclusion: BA has a preventing effect on diabetic nephropathy by amelioration of plasma albumin, BUN, Cr and renal histology changes during diabetic situation.