Is infliximab protective in testicular torsion/detorsion injury? NF-κB and MAPKs pathway (ERK1/2, JNK, p38 MAPK)

Aim: In this study, we aimed to investigate the effects of tumor necrosis factor-alpha (TNF-α) in testicular torsion/detorsion (TT/D) injury and whether the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways contribute to these effects, using the TNF-α inhibitor infliximab (INF).Material and Methods: Rats were randomly divided into three groups: Sham, T/D, and INF+T/D. Torsion was induced by rotating the right testis 720° clockwise, than the testis was fixed and maintained in that position for 3 hours. Ten minutes before detorsion, the rats were administered infliximab (5 mg/kg, i.p.) or the vehicle. Testicular weights were measured 2 and 24 hours after detorsion. Twenty-four hours after the detorsion procedure, the degree of histopathological damage to the testes was evaluated using the Cosentino score and immunostaining for MAPK pathways (JNK, p38 MAPK, and ERK1/2) and NF-κB.Results: In theT/D group, an increase in weight of testes and histopathological damage were observed. In this group, moderate intensity immunostaining was observed for NF-κB and ERK1/2 in spermatogenic cells, and strong immunostaining for JNK in spermatids, as well as for p38 MAPK in spermatocytes and sperm. INF treatment was not observed to reduce testicular weights, histopathological damage, and the intensity of immunostaining.Conclusion: This study presented that NF-κB and MAPK pathways, particularly JNK and p38 MAPK, are active in germ cells in TT/D injury. TNF-α inhibitor INF treatment did not show a protective effect in TT/D damage. Consequently, TNF-α inhibition alone may be insufficient to reduce TT/D damage and supress the activation of NF-κB and MAPKs.