Background: The widespread application of nanoparticles, such as titanium dioxide (TiO2), in daily products has raised concerns about their environmental and health impacts. High doses of TiO 2 nanoparticles can accumulate in the testes, causing oxidative stress, inflammation, and potential organ damage due to their small size and high reactivity. These particles may disrupt the blood-testis barrier, leading to sperm abnormalities through oxidative stress pathways. This study aimed to investigate the effect of Hesperidin, an antioxidant found in the citrus family, on the sperm parameters and serum biochemical factors in mice treated with Titanium dioxide nanoparticles. Materials and Methods: In this experimental study, twentyfour NMRI male mice were randomly divided into 4 groups: 1) control, 2) TiO2- NPs (100 mg/kg BW/day), 3) Hesperidin (100 mg/kg BW/day), 4) TiO2- NPs+ Hesperidin (100 mg/kg BW/ day) and treated orally for 35 days. All animals were anesthetized with ketamine and xylazine, and the epididymides were excised and placed in Ham's F10 for sperm parameter analysis (count, motility, viability, and abnormality). In addition, stress oxidative markers, including lipid peroxidation (MDA level) and total antioxidant capacity (TAC) (FRAP test), were assessed in blood serum. Data were analyzed using One-way ANOVA and Tukey’s test, and the means were considered significantly different at (P<0.05). Results: The group treated with TiO2- NPS showed a significant decrease in sperm count, motility, viability, and TAC level, and a significant increase in sperm abnormality and MDA level compared to the control group (P<0.05). The TiO2- NPs+Hesperidin group exhibited a significant increase in the sperm parameters and TAC level and a significant decrease in MDA level compared to the TiO2- NPs group (P<0.05). Conclusion: The results of this study indicated that hesperidin ameliorated the adverse effects of TiO 2 nanoparticles on sperm parameters and oxidative stress markers in mice.
