Thymoquinone effects on autophagy, apoptosis, and oxidative stress in cisplatin-induced testicular damage in mice.

PURPOSE: In this study, the effect of thymoquinone (TQ) on CP-induced spermatogenesis defects in mice has been investigated.

METHODS: Sperm parameters, serum testosterone concentration, histology, Bax/Bcl-2 ratio, and expression of autophagy-related biomarkers have been assessed. Total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in testicular tissue were examined for the evaluation of oxidative stress levels.

RESULTS: CP has induced histological changes and significantly increased the Bax/Bcl-2 ratio, decreased testosterone concentration, testicular weight, and sperm quality. CP induced oxidative stress by elevating OSI in the testicular tissue (p < 0.05). Expression of the autophagy-inducer genes (ATG7, ATG5, and Beclin-1) and ratio of LC3B/LC3A proteins were significantly decreased, while mTOR expression was increased in the CP group. TQ pretreatment dose-dependently decreased the Bax/Bcl-2 ratio and mTOR gene expression while increasing the expression of ATG5 and ATG7 genes, LC3B/LC3A ratio, and Beclin-1 proteins. TQ could also dose-dependently reverse the histology, testosterone level, and sperm quality of the CP-intoxicated mice.

CONCLUSIONS: These findings show that TQ pretreatment can enhance sperm production by inducing autophagy and reducing apoptosis and oxidative stress in the CP-intoxicated mouse testicles.