Diabetic nephropathy is a common cause for
end-stage renal disease. Present study investigated the beneficial role of
arjunolic acid (AA) against
streptozotocin (STZ) induced
diabetic nephropathy in rats. Diabetic renal injury was associated with increased kidney weight to
body weight ratio, glomerular area and volume, blood
glucose (
hyperglycemia),
urea nitrogen and serum
creatinine. This nephro pathophysiology increased the productions of
reactive oxygen species (ROS) and
reactive nitrogen species (RNS), enhanced lipid peroxidation, protein carbonylation and decreased intracellular
antioxidant defense in the kidney tissue. In addition,
hyperglycemia activates
polyol pathway by increasing
aldose reductase (AR) with a concomitant reduction in Na+-K+-
ATPase activity. Investigating the oxidative stress responsive signaling cascades, we found the activation of PKCdelta, PKCvarepsilon, MAPKs and
NF-kappaB (p65) in the renal tissue of the diabetic animals. Furthermore,
hyperglycemia disturbed the equilibrium between the pro and anti-apoptotic members of Bcl-2 family of
proteins as well as reduced mitochondrial membrane potential, elevated the concentration of cytosolic
cytochrome C and
caspase-3 activity. Treatment of AA effectively ameliorated diabetic renal dysfunctions by reducing oxidative as well as nitrosative stress and deactivating the
polyol pathways. Histological studies also support the experimental findings. Results suggest that AA might act as a beneficial agent against the renal dysfunctions developed in STZ-induced diabetes.