Inflammation and Oxidative Stress via Persistent Hyperglycemia in Progression of Diabetic Nephropathy in Type 2 Diabetes Mellitus

Abstract

Diabetic nephropathy is a major microvascular complication of diabetes, representing the leading cause of end stage renal disease in the world, and a major cause of morbidity and mortality in type 2 diabetic subjects. In the kidney, a number of pathways that generate reactive oxygen species (ROS) such as glycolysis, specific defects in the polyol pathway, uncoupling of nitric oxide synthase, xanthine oxidase, NAD (P) H oxidase, and advanced glycation have been identified as potentially major contributors to the pathogenesis of diabetic kidney disease. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins have been associated with diabetic nephropathy due to oxidative stress induced hyperglycemia. Oxidative stress in diabetes is responsible for endothelial dysfunction releasing inflammatory markers cytokines from the damaged renal tissue. Hyperglycemia induces intracellular reactive oxygen species in mesangial and tubular epithelial cells which induces cytokines, IL-6 and TNF-α production in glomerular mesangial and tubular epithelial cells in diabetic kidney. Antioxidants inhibit high glucose induced transforming growth factors and extra cellular matrix expression in glomerular mesangial and tubular epithelial cells, which ameliorate features of diabetic nephropathy, suggesting that oxidative stress plays an important role in diabetic renal injury causing diabetic nephropathy.

To Study the Effect of Zofenopril (Angiotensin Converting Enzyme Inhibitor) in Type 2 Diabetes Induced Nephropathy in Rats

“…The various mechanisms which are activated by hyperglycemia lead to changes such as mesangial cell proliferation, hypertrophy, modulation in the glomerular filtration rate, tissue damage of the renal endothelium, alterations in its membrane permeability, thickening of the basement membrane, activation of inflammatory responses, accumulation of extracellular matrix and increased cell matrix production. Hyperglycaemia may act through formation and accumulation of advanced glycation end products, activation of protein kinase C 10 , acceleration of the polyol pathway 11 , activation of hexosamine pathway 12 , and production of reactive oxygen species and over-expression of transforming growth factorβ 13 . Oxidative stress has been considered to be a common pathogenetic factor of the diabetic complications including nephropathy 14 .…”