فهرست نشریات علمی دسترسی آزاد ایران

Objective: Chronic tramadol (TRA) exposure has been reported to induce inflammatory responses in testicular tissue,whereas exercise training exerts immunomodulatory effects within the testes. Accordingly, this study investigatedwhether exercise training protocols (ETPs) during the post-withdrawal period modulate testicular inflammation via theTLR4/NF-κB–mediated inflammatory signaling pathway.Materials and Methods: In this experimental study, adult Wistar rats (n=36; sex: male; age: 8 weeks; body weight: 180-220g) were randomly assigned to a control group and tramadol-treated groups. The control group received normal saline. TRAwas administered at a dose of 40 mg/kg, via intraperitoneal route, for 60 days. TRA withdrawal was induced by stopping TRAadministration after 60 days and maintained for an additional 60 days. Following withdrawal, tramadol-exposed rats wereallocated to a withdrawal-only group or to low-, moderate-, or high-intensity continuous exercise training groups. At the end ofthe experimental period, testicular tissue samples were collected. The expression or levels of IL-6, IL-10, COX-II, TLR4, NF-κB,TNF-α, and iNOS parameters were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR),enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, immunofluorescence staining, and Western blottingmethods.Results: The TRA administration increased the expression of TLR4, NF-κB, IL-6, and TNF-α. These elevations werereduced after withdrawal and were more markedly attenuated in exercise-trained groups. IL-10 levels were decreasedin the tramadol-only group but were restored during withdrawal with exercise training. TRA exposure was associatedwith increased numbers of iNOS+ and COX-II+ somatic and germ cells; these alterations were reversed after withdrawal,particularly in exercised animals. Despite TRA cessation, residual immune dysregulation persisted, characterized byelevated TLR4, NF-κB, IL-6, and TNF-α expression.Conclusion: Exercise training following TRA withdrawal could restore inflammatory balance by suppressing TLR4 andNF-ΚB signaling, normalizing pro- and anti-inflammatory cytokine profiles, and possibly attenuating the iNOS/NO/COXIIpathway in Wistar rats.