Selenium protected NMRI mice against methotrexate induced testicular injury : Selenium effectiveness in methotrexate treated testis.

Methotrexate (MTX) is used to treat malignant and autoimmune disorders, while it also hurts testicular tissue leading to infertility. It has been shown that MTX induces testicular injury by producing oxidative stress, inflammatory cytokines, and apoptotic cascades, but its molecular mechanisms have not been fully investigated. Selenium (Se) with antioxidant properties is protective in testicular germ cells. The use of Se to modulate the oxidative stress caused by MTX was investigated in this study, focusing on P38 and NF-κB pathways in the testis of NMRI mice treated models with MTX. The control, MTX, Se, and MTX + Se groups were considered the male mice in this study. RNA extraction was utilized to examine the P38 and NF-κB gene expression by Real-time quantitative polymerase chain reaction (RT-qPCR). The testicular protein samples were extracted to analyze the protein expression of P38 and NF-κB. The assessment of TNF-α, IL-1β, and IL-6 levels was examined using ELISA. Tukey's tests and ANOVA were used for statistical analysis (p < 0.05). The increased significantly of P38 and NF-κB mRNA expression and up-regulation of P38 and NF-κB proteins were observed in the group treated with MTX compared to the control group while the administration of Se caused a significant decrease in the mRNA or proteins expression. The TNF-α, IL-6 and IL-1β protein expression in the following MTX treatment, in testis tissue, was raised significantly, and co-treatment with Se significantly reduced the testis tissue level of TNF-α, IL-6 and IL-1β protein in contrast to that of the MTX group. Our findings show the potential of Se as a medicine to modulate the destructive effects of MTX in testicular tissue which suggests Se supplementation as a viable method to prevent testicular damage from chemotherapy and maintain male fertility.