This study aimed at the effect of vitamin B12 (VB12) on tramadol (TRM) induced pituitary-gonadal Axis toxicity. Thirty-two (32) adult male rats were randomized into four groups of eight (n = 8) rats each. Group A served as control was given 1 ml normal saline, group B received 50 mg /kg bwt TRM, group C received 0.5 mg/kg bwt VB12 and group D received 50 mg /kg bwt TRM and 0.5 mg/kg bwt VB12 through gastric gavage daily for 8 weeks. Parameters tested include sperm parameter, male reproductive hormone, testicular histology, glucose, lactate dehydrogenase (LDH), acid phosphate (ACP), and alkaline phosphate (ALP) activity, steroidogenic protein, cytochrome P450 A1, nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor- kappa B (NF-κB), oxidative and antioxidant makers.
Tramadol significantly decreases sperm quality, hormone, steroidogenic protein, cytochrome P450 A1, ACP, ALP, and increases glucose, LDH, oxidative stress, mtTFA, and UCP2, p53 expression, NO, iNOS, NF-κB, IL-1β, IL-6, TNF-α, and caspase-3 activity. Degenerative alterations of the testes’ and pituitary architecture and perturbation of spermatogenesis were observed in TRM-treated rats. The intervention of VB12 downregulated testicular oxidative stress, inflammatory markers, glucose, lactate, LDH, p53, caspase-3, mtTFA, and UCP2. And upregulate antioxidant, sperm quality, hormone, and spermatogenic cells. Vitamin B12 exhibited mitigation against TRM–induced testicular dysfunction via its antioxidant, anti-inflammatory and anti-apoptotic effects.