LAUSR

HighlightsNesfatin‐1 reduced pro‐inflammatory cytokine expressions in torsioned rat testis.Apoptosis and seminiferous tubular degeneration were depressed by nesfatin‐1.Nesfatin‐1 elevated expressions of TGF‐&bgr; and reduced AKT and CREB in testis.Nesfatin‐1 ameliorated oxidative damage and preserved spermatogenic cells. ABSTRACT Testicular torsion causes ischemia‐reperfusion injury and an increased risk of infertility. Nesfatin‐1 is a novel peptide with antioxidant, anti‐inflammatory and anti‐apoptotic properties. In the present study, we aimed to investigate the putative beneficial effects of nesfatin‐1 on oxidative injury and impaired testicular function induced by testis torsion. Under anesthesia, male Sprague‐Dawley rats (180–230 g; n = 24) had sham‐operation or they underwent testicular torsion by rotating the left testis 720° and fixing it for 2 h, followed by a 2‐h detorsion. Rats in each group were treated intraperitoneally with either nesfatin‐1 (0.3 &mgr;g/kg) or saline prior to the torsion or sham‐torsion. At the end of the 4‐h experimental period, tissue samples were removed for evaluation of spermatozoa, molecular and histochemical analyses. In saline‐treated torsion/detorsion group, a high percentage of abnormal spermatozoa with head defects was observed, which was abolished in nesfatin‐1‐treated torsion/detorsion group. The levels of 8‐OHdG, tumor necrosis factor (TNF)‐alpha, interleukin (IL)‐6, caspase‐3 were increased in the saline‐treated torsion/detorsion group as compared to sham‐operated group, while nesfatin‐1 pre‐treatment significantly decreased the expressions of the pro‐inflammatory cytokines, depressed apoptosis, and also reduced the tubular degeneration. In addition, nesfatin‐1 in torsion/detorsion group elevated expressions of transforming growth factor (TGF)‐beta and reduced expressions of protein kinase B (AKT) and cAMP response element binding protein (CREB) in the testis tissue. The present findings show that nesfatin‐1, by regulating AKT and CREB signaling pathways and pro‐inflammatory/anti‐inflammatory cytokine balance, preserves the spermatogenic cells and ameliorates torsion‐detorsion‐induced tubular degeneration.