The Potential Protective Role of Ascorbic Acid Against Testicular Toxicity Induced by Fluoxetine in Male Wistar Rats.

Background: Fluoxetine (FLX) is a Selective Serotonin Re-uptake Inhibitor (SSRI) commonly used as a first-line treatment for depression, anxiety, and mood disorders. It can cause infertility in the male reproductive system through the release of Reactive Oxygen Species (ROS). This study aimed to evaluate the testiculo-protective potential of ascorbic acid against fluoxetine-induced spermatotoxicity in male Wistar rats. Methods: This study assessed Vitamin C's effect on male fertility in fluoxetine-treated Wistar rats. Thirty rats (130 ± 40 g) were divided into six groups (n=5): Control (distilled water), fluoxetine 20 mg/kg, Vitamin C 100 mg/kg, fluoxetine 20 mg/kg + Vitamin C 50 mg/kg, fluoxetine 20 mg/kg + Vitamin C 100 mg/kg, and fluoxetine 20 mg/kg + Vitamin C 150 mg/kg. Treatments were administered daily via oral gavage for 60 days, followed by assessments of testicular weight, semen analysis, oxidative stress biomarkers (CAT and GPx), and histomorphology. The data was analyzed using one-way ANOVA and Turkey's post-hoc multiple comparison test, reporting as mean±SEM using The GraphPad Prism version 6.0 for Windows, with significance set at p<0.05. Results: Vitamin C, administered particularly at higher doses, significantly increased body weight, testicular weight, and antioxidant enzyme levels (glutathione peroxidase and catalase) while improving fertility parameters such as sperm count, motility, and viability in treated rats (P<0.05). Fluoxetine alone led to a significant reduction (P<0.05) in these parameters, but the combination with Vitamin C mitigated these effects. Histological analysis showed improved testicular structure in Vitamin C-treated groups, highlighting its protective role against fluoxetine-induced testicular damage. Conclusion: Ascorbic acid has testiculoprotective potential in fluoxetine-induced spermatotoxicity, mainly owing to its antioxidant properties.