Prophylactic role of arjunolic acid in response to streptozotocin mediated diabetic renal injury: activation of polyol pathway and oxidative stress responsive signaling cascades.
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.
Manna
Prasenjit
P
Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata 700054, West Bengal, India.
Sinha
Mahua
M
Sil
Parames C
PC
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D003928:Diabetic Nephropathies / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D011108:Polymers / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013311:Streptozocin / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D011108:Polymers; D017382:Reactive Oxygen Species; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C024617:polyol; D009569:Nitric Oxide; C061640:arjunolic acid; D013311:Streptozocin; D011494:Protein Kinases