Received July 08, 2025
Accepted February 20, 2026

Objective: Cisplatin (CIS), a platinum-based chemotherapeutic, is highly effective in cancer treatment but often leads to severe adverse effects, including testicular damage and infertility. The oxidative stress and inflammation induced by CIS result in disrupted spermatogenesis, decreased testosterone levels, and testicular apoptosis, primarily mediated by elevated reactive oxygen species (ROS), pro-inflammatory cytokines, and activation of pathways like NF-κB and p38 MAPK. This study explores the protective role of naringenin (NG), a flavonoid with antioxidant, anti-inflammatory, and anti-apoptotic properties, in mitigating CIS-induced testicular damage in a murine model. Methods: Male mice were divided into control and CIS-, NG-, and NG+CIS-treated groups. Key outcomes included serum testosterone levels, oxidative stress markers, inflammatory mediators, Bax/Bcl-2 expression, histopathological evaluations, and morphometric analyses. Results: NG treatment attenuated CIS-induced oxidative stress by normalizing total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) levels while reducing pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and NF-κB activation. NG also modulated apoptotic pathways by restoring the balance of Bax/Bcl-2 and suppressing p38 MAPK activation. Histological assessments revealed improved seminiferous tubule morphology and spermatogenesis in the NG+CIS group. Conclusion: NG effectively counteracts CIS-induced testicular toxicity, highlighting its therapeutic potential in preserving male fertility during chemotherapy by mitigating oxidative, inflammatory, and apoptotic damage.