An Assessment of the Effects of Vitamin A on Biochemical Indices, Sperm Parameters and Testicular Morphology in 5-Fluorouracil-treated Male Rats

Oladipupo Boluwatife Mary¹, Ajao Joshua Aduragbemi¹, Akinsehinwa Akinsanmi Festus², Famuyide Opeyemi Ojo² Onaolapo Adejoke Yetunde^{2, 3} Onaolapo Olakunle James^1,4

1. Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria
2. Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
3. Behavioural Neuroscience and Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria, orcid.org/0000-0001-7126-7050
4. Behavioural Neuroscience and Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria, orcid.org/0000-0003-2142-6046

ABSTRACT

Chemotherapeutic agents like 5-Fluorouracil (5-FU) are useful in cancer management, but they are known to be associated with adverse effects, including subfertility in male patients. Such adverse effects may limit clinical application, necessitating the search for agents that can reduce them. This study evaluated the possible protective effect of Vitamin A against 5-FU-induced fertility impairment in male rats. Sixty male Wistar rats (150–170 g each) were randomly assigned to six groups (n=10). Group A received normal saline orally at 10 ml/kg, while Groups B and C received Vitamin A at 500 IU/kg and 1000 IU/kg, respectively. Group D received a single dose of 5-FU (50 mg/kg) intraperitoneally. Groups E and F were co-treated with 5-FU and Vitamin A at 500 IU/kg and 1000 IU/kg, respectively, for 14 days. After treatment, rats were euthanised, and blood samples were collected for the estimation of interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), total antioxidant capacity (TAC), and malondialdehyde (MDA). Body weight, feed intake, and sperm parameters (count, motility, morphology) were assessed. Testes and epididymes were harvested for histological evaluation. Data were analysed using One-way ANOVA and Tukey’s Honestly Significant Difference (HSD) test; with statistical significance set at p<0.05. Results indicated that Vitamin A, especially at 1000 IU/kg, attenuated 5-FU-induced oxidative stress and reproductive toxicity, highlighting its potential as a protective agent against chemotherapy-induced subfertility. The 5-FU group had lower body weight, reduced food intake, decreased total antioxidant capacity, and elevated lipid peroxidation. Co-treatment with Vitamin A improved these parameters, restored IL-10 levels, and reduced TNF-α expression. Sperm quality and testicular structure were also better preserved in the Vitamin A-treated groups. However, further studies are needed to establish this.

KEYWORDS: Antioxidants, Beta-carotene, Chemotherapy, Infertility, Oxidative Stress, Retinol