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

Abstract

Joshua Ojodale Aruwa,1 Sunday Agba Bisong,2 Kebe Obeten,3 Ekom Monday Etukudo,4 Neeza Timothy,1 Theophilus Gbednet Kureh,5 Godwin Aiyabalu Okoruwa,6 Theophilus Pius,7 Ibe Michael Usman4 1Department of Pharmacology and Toxicology, Kampala International University, Bushenyi, Uganda; 2Department of Physiology, University of Calabar, Calabar, Nigeria; 3Department of Human Anatomy, Lusaka Apex Medical University, Lusaka, Zambia; 4Department of Human Anatomy, Kampala International University, Bushenyi, Uganda; 5School of Pharmacy, Eden University, Lusaka, Zambia; 6Department of Pharmacy, Kampala International University, Dar Es Salaam, Tanzania; 7Medical Laboratory Science Department, Kampala International University, Bushenyi, UgandaCorrespondence: Ibe Michael Usman, Email [email protected]: 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.Keywords: testiculo-protection, oxidative stress, histomorphology, spermatotoxicity, ascorbic acid, vitamin C, male fertility

Keywords

• testiculo-protection
• oxidative stress
• histomorphology
• spermatotoxicity
• ascorbic acid
• vitamin c
• male fertility.