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 streptozotocinnicotinamide
(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.