Background: Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is widely used in the treatment of neurological disorders. However, its application carries the risk of adverse reactions, including reproductive toxicities. Grape seed is highly regarded for its pharmacological activities, specifically its antioxidant properties. Objectives: This study was designed to evaluate whether hydroalcoholic grape seed extract (GSE) could ameliorate FLX-evoked oxidative injuries in the mouse testis. Materials and Methods: Thirty-two male mice were categorized into four groups of eight mice each. Two groups received FLX at a dose of 20 mg/kg per day over a period of six weeks by oral gavage. One of these groups received GSE at a dose of 100 mg/kg per day orally along with the FLX. An untreated control group and a GSE-only treated group were also included. Serum and testicular samples were collected 24 hours after the last treatment. Results: Biochemical analyses demonstrated that FLX caused significant decreases in testicular antioxidant capacity and serum testosterone concentrations, as well as lipid peroxidation elevations in testicular tissue. Morphometric and histopathological studies supported the biochemical findings. Concomitant administration of GSE with FLX markedly reduced testicular damage and significantly restored all of the mentioned markers to normal values. Conclusions: The findings suggested that oxidative stress-mediated testicular damage, arising as a result of FLX administration in mice, could be reversed by GSE.
