L-Carnitine and vitamin E mitigate morphine-induced testicular damage in NMRI mice: Association with altered superoxide dismutase ۱ and histone deacetylase ۱/۲ expression: An experimental study

Background: Morphine (MOR) induces testicular injury via oxidative stress. Vitamin E (Vit E) and L-carnitine (LC) may counteract this through antioxidant activity. Objective: To investigate individual and combined effects of Vit E and LC on testicular superoxide dismutase (SOD) activity, as well as SOD۱ and histone deacetylase (HDAC) ۱/۲ expression. Materials and Methods: In this experimental study, ۳۴ male NMRI mice (۶-۸ wk, ۲۸-۳۰ gr) were divided into vehicle (normal saline) and MOR (gradually increasing MOR doses) groups. After excluding ۴ dependent mice confirmed by naloxone on day ۱۰, the remaining animals (n = ۶/group) received ۳۵ days of treatment with either MOR alone or combined with LC, Vit E, or both. The testes were collected for histology, SOD activity, and gene expression analysis. Results: Chronic MOR use led to a lower Johnson's score, wider lumen diameter, thinner epithelium (p < ۰.۰۰۱), and increased HDAC۱ expression (۶.۰۲ ± ۰.۳۱, p < ۰.۰۱), with non-significant decreases in SOD۱ expression (۰.۴۴ ± ۰.۰۲) and SOD activity (۲۵.۲۵ ± ۳.۷۹) compared to the vehicle group. LC and Vit E attenuated these changes; their combination showed superior improvement in histomorphometry (p < ۰.۰۰۱), elevating SOD۱ expression (۲.۴۰ ± ۰.۳۵, p < ۰.۰۱) and SOD activity (۸۷.۷۵ ± ۱۶.۲۶, p < ۰.۰۵), while reducing HDAC۲ expression (۰.۵۲ ± ۰.۰۶, p < ۰.۰۵). Conclusion: SOD۱ regulation appears key in testicular antioxidant defense. MOR reduced SOD۱ and damaged testes; LC and Vit E, especially combined, mitigated these effects. The association between altered histone modifier expression and SOD۱ mRNA suggests a possible epigenetic link in oxidative stress -induced testicular damage; however, protein and functional-level studies are needed.

کلیدواژه ها:

Morphine ، L-carnitine ، Vitamin E ، Superoxide dismutase ۱ ، Histone deacetylase ، Testis. ، مورفین ، ال-کارنیتین ، ویتامین E ، سوپراکسید دیسموتاز ۱ ، هیستون داستیلاز ، بیضه.