Amelioration of Diabetic Nephropathy Using Ellagic Acid-encapsulated Zinc Nanoparticles Through the modulation of Oxidative Stress and Inflammatory Signaling in Rats

A significant contributor to the onset and advancement of diabetic microvascular problems, such as nephropathy, is the inflammation and oxidative stress caused by hyperglycemia in diabetes mellitus. Goals: To examine the biochemical, molecular, and histopathological effects of ellagic acid-loaded zinc nanoparticles (EA-ZnNPs) on inflammation-induced diabetic nephropathy and oxidative stress. Forty albino male rats served as subjects in this study. They were randomly assigned to one of four groups: control, streptozotocin (STZ) diabetic group without treatment, STZ-diabetic treated with ellagic acid-loaded zinc nanoparticles (EA-ZnNPs), and STZ-diabetic treated with insulin. Serum glucose, urea, and creatinine levels were significantly elevated after STZ injection from a biochemical perspective. There was a substantial drop in insulin, albumin, renal tissue glutathione peroxidase (GPX), and catalase (CAT), and an increase in renal tissue malondialdehyde (MDA) and Nitric Oxide (NO). Molecularly, the expression of nuclear factor kappa beta (NF-Kb) and matrix metalloproteinases-9 (MP9) in kidneys was elevated. In contrast, interleukin 10 (IL-10), Peroxisome proliferator-activated receptor-gamma (PPAR-γ), heme oxygenase-1HO-1 are decreased. Histopathologically, STZ administration resulted in diabetes, as revealed by severe congestion of renal parenchyma blood vessels, tubular atrophy, hemorrhage, and focal aggregation of lymphocytic cells in interstitial tissue, along with decreased number and size of islet cells in the pancreas, vacuolar degeneration of islet cells, and vacuolar degeneration of exocrine acini. By enhancing biochemical, molecular, and histopathological alterations, EA-ZnNP treatment mitigates the harmful consequences of STZ administration. Finally, EA-ZnNPs have a protective function against diabetic nephropathy progression via antihyperglycemic, antioxidant, and anti-inflammatory effects when administered orally.