فهرست نشریات علمی دسترسی آزاد ایران

Background: The study investigated how exercise training protocols (ETPs) with different intensities can amelioratethe tramadol (TRA)-induced toxicity in the testicular tissue by upregulating VEGF/VEGFRs/PI3K/AKT signalingpathway in the post-withdrawal period.Materials and Methods: In this experimental study, thirty-six mature Wistar rats were included in two groups: onebeing a sedentary control group, and the other receiving TRA treatment (40 mg/kg, daily, ip). After 60 days, six ratsfrom the TRA-received group were excluded (TRA-sole; euthanized after 60 days). The TRA administration wasstopped and the rats were further divided into four subgroups: TRA/withdrawal (TRA/W), low (LICT), moderate(MICT), and high (HICT)-intensity continuous exercise training-received groups (n=6/each group). The expressionlevels of phosphoinositide 3-kinases (PI3K), protein Kinase B (AKT), vascular endothelial growth factor (VEGF),VEGF receptor 1 (VEGF R1) and 2 (VEGF R2) were assessed.Results: The expression levels of PI3K, AKT, VEGF, VEGF R1, and VEGF R2 were decreased in the TRA-solegroup. No significant alterations were noted in the PI3K, AKT, VEGF, and VEGF R1 expressions after 60 days ofwithdrawal compared to the TRA-sole rats. However, this situation was reversed and the expression levels of PI3K,AKT, VEGF, VEGF R1, and VEGF R2 increased in the MICT and HICT-received groups.Conclusion: TRA disrupts the PI3K/AKT interaction, and this disruption is not easily reversed shortly after withdrawal.However, ETPs exert positive effects on PI3K/AKT signaling by promoting the expression of VEGF, VEGFR1,and R2. These results highlight the potential of ETPs to ameliorate the adverse effects of TRA on VEGF/VEGF R1,R2/PI3K/AKT signaling, even a short time after withdrawal.