Ameliorative Effects of Ginger-Zinc Oxide Nanoparticles on Lead Nitrate-Induced Oxidative Stress in  Wistar Rats

Lead exposure disrupts male reproductive health, however, natural antioxidants and trace elements may offer protection against such effects. This study investigated the protective efficacy of ginger-zinc oxide nanoparticles (G-ZO Nps) against lead nitrate-induced testicular toxicity in Wistar rats. Zinc oxide nanoparticles were synthesized and characterized by Ultraviolet-Visible (UV-VIS) spectroscopy, Fourier Transformed Infrared Spectroscopy (FTIR), Scanning Electron Microscopy-Energy Dispersive X-ray Spectroscopy (SEM-EDX), and High-Performance Liquid Chromatography (HPLC). Twenty rats were divided into five groups: control, lead nitrate, ginger extract, G-ZO Nps, and zinc acetate. Treatments lasted 28 days via oral gavage, after which testicular tissues were subjected to biochemical, and histological analyses. Moreover, in silico molecular docking was conducted on twelve G-ZO Nps derived flavonoids and zinc acetate against three reproductive proteins using AutoDock Vina, with ligand-protein interactions visualized via Discovery Studio Visualizer. SwissADME was also employed to assess pharmacokinetic and drug-likeness profiles. Lead nitrate markedly suppressed superoxide dismutase (SOD) and catalase (CAT) activities, slightly elevated glutathione peroxidase (GPx) and glutathione (GSH) levels, demonstrated no effect on malondialdehyde (MDA) levels, significantly increased nitric oxide (NO) levels, and caused degeneration of seminiferous tubules. G-ZO Nps restored antioxidant balance and preserved testicular histoarchitecture more effectively than ginger extract or zinc acetate. Molecular docking identified apigenin, isoquercetin, and myricetin 3-O-galactoside as the most stable flavonoids (–9.8 to –9.9 kcal/mol), with superior drug-likeness and bioavailability confirmed by SwissADME, while zinc acetate showed weak binding. It can be concluded that G-ZO Nps demonstrated potent antioxidative and histoprotective effects against lead-induced testicular injury, surpassing both ginger extract and zinc acetate. These findings position Z. officinale nanoparticles as a promising nanotherapeutic strategy for mitigating heavy metal–induced reproductive toxicity.