Synergistic effects of zinc oxide nanoparticles and chitosan on diabetic nephropathy rat models

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes mellitus (DM), strongly linked to hyperglycemia-induced oxidative stress. This study evaluated the therapeutic effects of zinc oxide nanoparticles (ZnO NPs), chitosan, and their combination on glycemic control, renal function, and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Fifty male rats were divided into five groups (n = 10): control, diabetic, ZnO NP-treated (10 mg/kg), chitosan-treated (200 mg/kg), and combination-treated. DN was induced via STZ (50 mg/kg, i.p.). After treatment for nine weeks, blood glucose, glycosylated hemoglobin (HbA1c), insulin, renal biomarkers (urea, uric acid, creatinine), and antioxidant markers glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were measured, alongside histological kidney examination. Diabetic rats exhibited significant metabolic and renal dysfunction: blood glucose increased from 95.72 ± 0.44 to 284.08 ± 0.76 mg/dL, HbA1c from 4.66 ± 0.06 to 17.35 ± 0.13%, and insulin decreased from 21.50 ± 0.65 to 3.09 ± 1.00µIU/mL. Combination treatment restored these parameters nearly to control levels: glucose (97.64 ± 3.28 mg/dL), HbA1c (4.62 ± 0.14%), and insulin (21.88 ± 0.41 µIU/mL). Renal dysfunction markers were significantly elevated in diabetic rats, including urea (46.01 ± 0.28 mg/dL), uric acid (8.09 ± 0.19 mg/dL), and creatinine (1.79 ± 0.06 mg/dL). Combined treatment reduced these renal biomarkers toward normal levels, and antioxidant defense was restored: GSH increased from 3.26 ± 0.10 to 16.08 ± 0.29 nmol/mg, MDA decreased from 1.34 ± 0.10 to 0.34 ± 0.01 nmol/mg, SOD increased from 99.83 ± 0.33 to 173.95 ± 0.52 U/mg, and CAT from 82.14 ± 0.18 to 119.71 ± 0.48 U/mg. Histological improvements included normalization of glomerular and tubular architecture. Combined ZnO NPs and chitosan therapy markedly ameliorated hyperglycemia, oxidative stress, and renal dysfunction in diabetic rats. These findings support their potential as synergistic nephroprotective agents against DN.