Thyroid hormones play essential roles in spermatogenesis, but their effects on infertile males remain poorly understood. This study aimed to evaluate the impact of combining carbimazole (CBZ) with vitamin E (VE) on testicular injury induced by experimental hyperthyroidism in adult albino rats, focusing on oxidative, inflammatory, and apoptotic pathways. In this experimental study, 64 adult male albino Wistar rats were divided into eight groups: Group I (control-untreated), Group II (CBZ-control), Group III (VE-control), Group IV (CBZ + VE-control), Group V (levothyroxine-induced testicular injury), Group VI (levothyroxine + CBZ-treated), Group VII (levothyroxine + VE-treated), and Group VIII (levothyroxine + CBZ + VE-treated). The study was conducted in the Faculty of Medicine, Suez Canal University (Ismailia, Egypt). After cervical decapitation, both testes and epididymis were examined histopathologically and immunohistochemically. Significant differences were observed among groups concerning malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT; all P < 0.001). Polymerase chain reaction analysis showed significant differences in tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), Bcl-2-associated X protein (BAX), B-cell lymphoma 2 protein (Bcl2), p53, Caspase-3, Caspase-8, Caspase-9, and nuclear factor-kappa B (NF-κB) mRNA levels (all P < 0.001). Hyperthyroid group treated with CBZ alone (Group VI) exhibited testicular side effects, affecting seminiferous tubules and spermatogenesis. However, the Group VIII showed improved spermatogenesis and a decrease in testicular side effects. The addition of VE to the treatment of hyperthyroid rats with CBZ reduced testicular side effects and seminiferous tubular affection when potentially improving spermatogenesis. Further research is needed to elucidate the underlying mechanisms fully.

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