The effects of infliximab on NF-KB, MAP kinases and HSP70 on testicular torsion detorsion injury in rats

The purpose of the present study, the effects of tumor necrosis factor-alpha (TNF-α) in testicular torsion/detorsion (T/D) injury and whether there is a contribution of nuclear factor kappa B (NF-kB), mitogen activated protein kinase (MAPK) pathways and heat shock protein 70 (HSP70) in these effects to investigate using infliximab (INF) as a TNF-α inhibitor. Rats were divided into 3 groups as SHAM, T/D and INF+T/D. Torsion was created by rotating the right testis 720° clockwise and maintained by fixing the testis for 3 hours. The rats were treated with infliximab 5 mg/kg (i.p.) and vehicle, at 10 min prior detorsion. Two and 24 hours after detorsion, weights of testes were measured. At the 2nd hour of detorsion, HSP70 levels were measured in the testes. At the 24th hour of detorsion, histopathological damage and MAPKK activated JNK, p38 MAPK and ERK pathways and NF-kB was evaluated in the testes. In the testis with T/D; there was the weight increase at the 2nd hour of detorsion and an increase in the histopathological damage at 24th hours of detorsion. After 2 hours of detorsion, levels of HSP70 in testicular tissue were not different from those of SHAM group. INF did not effected on testis weights, histopathological damage and HSP70 levels. At the 24th hour of detorsion, T/D application was observed to cause the İmmünological staining at the middle intensity NF-kB and ERK1/2 in spermatogenic cells and at the severe intensity JNK in the spermatids close to seminiferous tubule lümen and p38 MAPK in the sperm in lumen and close lumen in spermatocytes. However it was observed that INF treatment did not reduce the severity of İmmüne staining. This study demonstrated that NF-kB and MAPK pathways, especially JNK and p38 MAPK, are active in germinal cells in testicular T/D injury. It was that not reduced T/D injury by INF was showed TNF-α does not act alone in the activation of these proteins in testicular T/D injury. Keywords: Testicular torsion/detorsion, TNF-α inhibitor, Infliximab, MAP kinaz pathways, NF-κB, JNK, ERK, p38 MAPK, HSP70