Zinc Oxide Nanoparticles and Chitosan Exhibited Synergistic Protection Against Diabetic Nephropathy in Mice Model

Diabetic nephropathy (DN) is a progressive complication of diabetes mellitus characterized by oxidative stress, impaired glucose metabolism, and renal dysfunction. This study explored the protective effects of zinc oxide nanoparticles (ZnO NPs), chitosan, and their synergism on renal function disorders, oxidative stress, and histopathological alterations in a streptozotocin (STZ)-induced diabetic mice model. Mice treated with STZ exhibited marked hyperglycemia (284.08 ± 0.76 mg/dL), elevated HbA1c (17.35 ± 0.13%), and reduced insulin levels (3.09 ± 1.00 μI/mL), along with increased levels of renal biomarkers: urea (46.01 ± 0.28 mg/dL), uric acid (8.09 ± 0.19 mg/dL), and creatinine (1.79 ± 0.06 mg/dL). Antioxidant defense was compromised, as indicated by reduced GSH (3.26 ± 0.10 μmol/g), SOD (99.83 ± 0.33 U/mg), and CAT (82.14 ± 0.18 U/mg), with elevated MDA levels (1.34 ± 0.10 nmol/mg). Treatment with ZnO NPs and chitosan, individually and in combination, significantly improved all parameters. The combination treatment showed superior efficacy, restoring glucose (97.64 ± 3.28 mg/dL), HbA1c (4.62 ± 0.14%), insulin (21.88 ± 0.41 μIU/mL), and reducing urea (14.03 ± 0.22 mg/dL), uric acid (5.61 ± 0.27 mg/dL), and creatinine (0.56 ± 0.01 mg/dL). Oxidative stress was ameliorated, with GSH (16.08 ± 0.29 ng/ml), SOD (173.95 ± 0.52 U/ml), CAT (119.71 ± 0.48 Mu/L), and MDA (0.34 ± 0.01 nmol/ml) approaching control levels. Histopathological analysis confirmed renal tissue restoration. These findings demonstrate a novel synergistic nephroprotective effect of ZnO NPs and chitosan, primarily through antioxidant enhancement and renal biomarker normalization, highlighting their potential as therapeutic agents for DN management.