Small Molecule Inhibiting NF-kB Ameliorates Oxidative Stress and Suppresses Renal Inflammation in Early Stage of Alloxan-induced Diabetic Nephropathy in Rat.
Basic Clin Pharmacol Toxicol. 2016 Nov 26. Epub 2016 Nov 26. PMID: 27888584
Manash P Borgohain
Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus which ultimately gives rise to cardiovascular diseases. Oxidative stress produced by prolonged hyperglycaemia and chronic renal inflammation are the two key players in the development and progression of diabetic nephropathy. NF-kB-mediated inflammatory cascade is a strong contributor to the renovascular inflammation in diabetic nephropathy. Here, we studied the effects of piceatannol, a potent NF-kB inhibitor, on various oxidative stress markers and diabetic renal inflammatory pathway in rat induced by alloxan. Experimental diabetes was induced in male Wistar rats by a single intraperitoneal dose, 150 mg/kg body weight (b.w.) of alloxan. Treatment with piceatannol to diabetic rats was given in two doses, i.e. 30 and 50 mg/kg b.w. After 14 days of oral treatment, piceatannol significantly restored blood sugar level, glomerular filtration rate (GFR), serum markers and plasma lipids. PCTNL administration also reversed the declined activity of cellular antioxidant machineries namely superoxide dismutase (SOD) and glutathione (GSH), and the elevated levels of melondialdehyde (MDA) and nitric oxide (NO). Moreover, piceatannol-treated groups showed marked inhibition of renal pro-inflammatory cytokines and NF-kB p65/p50 binding to DNA. Renal histopathological investigations also supported its ameliorative effects against diabetic kidney damage. Importantly, effects were more prominent at a dose of 50 mg/kg and in terms of body weight gain, piceatannol failed to effect significantly. However, overall findings clearly demonstrated that piceatannol provides remarkable renoprotection in diabetes by abrogating oxidative stress and NF-kB activation - and might be helpful in early stage of diabetic nephropathy. This article is protected by copyright. All rights reserved.