L-Carnitine and vitamin E mitigate morphine-induced testicular damage in NMRI mice: Association with altered superoxide dismutase 1 and histone deacetylase 1/2 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 SOD1 and histone deacetylase (HDAC) 1/2 expression. Materials and Methods: In this experimental study, 34 male NMRI mice (6–8 wk, 28–30 gr) were divided into vehicle (normal saline) and MOR (gradually increasing MOR doses) groups. After excluding 4 dependent mice confirmed by naloxone on day 10, the remaining animals (n = 6/group) received 35 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 < 0.001), and increased HDAC1 expression (6.02 ± 0.31, p < 0.01), with non-significant decreases in SOD1 expression (0.44 ± 0.02) and SOD activity (25.25 ± 3.79) compared to the vehicle group. LC and Vit E attenuated these changes; their combination showed superior improvement in histomorphometry (p < 0.001), elevating SOD1 expression (2.40 ± 0.35, p < 0.01) and SOD activity (87.75 ± 16.26, p < 0.05), while reducing HDAC2 expression (0.52 ± 0.06, p < 0.05). Conclusion: SOD1 regulation appears key in testicular antioxidant defense. MOR reduced SOD1 and damaged testes; LC and Vit E, especially combined, mitigated these effects. The association between altered histone modifier expression and SOD1 mRNA suggests a possible epigenetic link in oxidative stress-induced testicular damage; however, protein and functional-level studies are needed.