Abstract
BACKGROUND AND AIM: Diabetic nephropathy (DN) is a major complication of diabetes mellitus characterized by oxidative stress and inflammation. Conventional treatments often fail to prevent its progression. This study investigates the therapeutic potential of Tithonia diversifolia zinc oxide nanoparticle emulsion (TDNP) in mitigating DN by enhancing antioxidant and immunomodulatory mechanisms. This study aimed to evaluate the effect of TDNP on oxidative stress markers, inflammation, and insulin activity in streptozotocin (STZ)-induced DN rats. MATERIALS AND METHODS: Male Wistar rats (n = 24) were divided into four groups: control (saline), positive control (0.1% zinc oxide suspension), treatment (TDNP at 100 mg/kg body weight), and comparison (quercetin at 5 mg/kg body weight). DN was induced using STZ and nicotinamide. Blood glucose, creatinine, urea, gamma-glutamyl transferase (γ-GT), and high-density lipoprotein cholesterol levels were assessed. Oxidative stress markers (superoxide dismutase [SOD], glutathione peroxidase [GPx]), inflammatory cytokines (TNF-α), and immunohistochemical indicators (anti-insulin, interferon-gamma [IFN-γ]) were measured. Data were analyzed using a one-way analysis of variance and Kruskal-Wallis tests. RESULTS: TDNP treatment significantly reduced blood glucose, creatinine, urea, γ-GT, and TNF-α levels (p ≤ 0.05), while increasing SOD, GPx, and anti-insulin levels compared with the positive control. Histopathological analysis showed decreased necrosis and inflammation in pancreatic and renal tissues. Immunohistochemistry revealed enhanced anti-insulin and reduced IFN-γ expression in TDNP-treated rats, indicating improved immune regulation and oxidative stress mitigation. CONCLUSION: TDNP demonstrates potent antioxidative and anti-inflammatory effects, effectively improving glucose metabolism and kidney function in DN. These findings highlight TDNP as a promising therapeutic agent for managing DN.