Protective Effects of Thiamine on Histomorphometric and Histochemical Changes in Testicular Tissue in Mice Under Oxidative Stress Induced by Methotrexate Treatment

Background: One of the important side effects of methotrexate (MTX) is its toxic effects on testicular tissue. In contrast, thiamine has been shown to have a therapeutic impact on cellular stress. Objectives: The present cross-group comparative study aimed to evaluate the protective effect of thiamine against MTX-induced oxidative stress. Methods: For the study, 36 mice were randomly divided into 6 equal groups. The first healthy control group received normal saline intraperitoneally (IP), the second sham control group received MTX 10 mg/kg/week, IP, the third control positive group received vitamin B1 100 mg/kg/week, IP, and groups 4, 5, and 6 received MTX + VitB1 25, 50, and 100 mg/kg/day, IP, respectively. Thirty-six days after the start of treatment, testicular tissue samples were taken by euthanizing the mice and used for biochemical and histological examination. All data were analyzed using one-way ANOVA and a Bonferroni post-hoc test. Results: The present study showed that the levels of caspase and malondialdehyde in the sham control group increased, and the total antioxidant capacity (TAC) decreased. Also, the mean number of germinal epithelial layers, primary spermatocyte cells, Leydig cells, active Sertoli cells, spermatogenesis indices and Johnsen Score Index decreased, but the average number of mast cells increased. The use of vitamin thiamine with MTX dose-dependently had protective effects, especially at 100 mg/kg, and improved the parameters above. Conclusions: The present study showed that thiamine, among the three doses, at 100 mg/kg, has the most significant protective effects against MTX-induced oxidative stress.