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

İnfliksimab testiküler torsiyon/detorsiyon hasarında koruyucu mu? NF-ĸB ve mapk yolakları (ERK1/2, JNK, p38 MAPK)

Ebru Kocakayaa(Zonguldak Bülent Ecevit University, Institute of Health Sciences, Pharmacology Master's Programme, Zonguldak, Türkiye)0009-0005-2971-8440
Günnur Özbakiş Dengiz(Zonguldak Bülent Ecevit University, Faculty of Medicine, Department of Medical Pharmacology, Zonguldak, Türkiye)0000-0000-0311-1735
Zehra Yılmaz(Harran University, Faculty of Medicine, Department of Medical Pharmacology, Şanlıurfa, Türkiye,)0000-0002-9523-7718
Meryem Akpolat Ferah(Zonguldak Bülent Ecevit University, Faculty of Medicine, Department of Histology and Embryology, Zonguldak, Türkiye)0000-0002-3419-1728
Kanat Gülle(Süleyman Demirel University, Faculty of Medicine, Department of Histology and Embryology, Isparta, Türkiye)0000-0002-6337-8962
Pages
289–299
Publication Date
2026-08-31
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Consequently, TNF-α inhibition alone may be insufficient to reduce TT/D damage and supress the activation of NF-κB and MAPKs.

📌 3 Key Takeaways

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Objective & Hypothesis: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).
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Key Findings & Data:Torsion was induced by rotating the right testis 720° clockwise, than the testis was fixed and maintained in that position for 3 hours.
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Conclusion & Impact:Consequently, TNF-α inhibition alone may be insufficient to reduce TT/D damage and supress the activation of NF-κB and MAPKs.
🔬Design:Araştırma Makalesi
📍Scope:Comprehensive Sample
⚙️Variables:Testiküler torsiyon/detorsiyon · TNF-α inhibitörü · infliksimab

Abstract

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.

Özet

Amaç: Bu çalışmada, TNF-α inhibitörü infliksimab (INF) kullanarak, testis torsiyonu/detorsiyonu (TT/D) yaralanmasında tümör nekroz faktörü-alfa (TNF-α) etkilerini ve nükleer faktör kappa B (NF-κB) ve mitojenle aktive olan protein kinaz (MAPK) yolaklarının bu etkilere katkıda bulunup bulunmadığını araştırmayı amaçladık. Gereç ve Yöntemler: Sıçanlar 3 gruba ayrıldı: Sham, T/D ve INF+T/D. Torsiyon, sağ testisin saat yönünde 720° döndürülmesiyle oluşturuldu ve testis 3 saat boyunca sabitlendi ve korundu. Sıçanlar, detorsiyondan 10 dakika önce 5 mg/kg infliksimab (i.p.) veya çözücüsü ile tedavi edildi. Torsiyonun giderilmesinden 2 ve 24 saat sonra testis ağırlıkları ölçüldü. Torsiyonun giderilmesinden 24 saat sonra, testislere verilen histopatolojik hasarın derecesi Cosentino skoru ve MAPK yolakları (JNK, p38 MAPK ve ERK1/2) ve NF-κB için immüno boyama kullanılarak değerlendirildi. Bulgular: T/D grubunda testis ağırlığında artış ve histopatolojik hasar gözlendi. Bu grupta, spermatogenez hücrelerinde NF-κB ve ERK1/2 için orta yoğunlukta immüno boyama, spermatidlerde JNK için şiddetli yoğunlukta immüno boyama ve spermatositlerde ve spermlerde p38 MAPK için şiddetli yoğunlukta immüno boyama gözlendi. INF tedavisinin testis ağırlıklarını, histopatolojik hasarı ve immüno boyama yoğunluğunu azalttığı gözlenmedi. Bu çalışma, NF-κB ve MAPK yolaklarının, özellikle JNK ve p38 MAPK'nin, TT/D hasarında germ hücrelerinde aktif olduğunu göstermiştir. TNF-α inhibitörü INF tedavisi, TT/D hasarında koruyucu bir etki göstermemiştir. Sonuç: TNF-α inhibisyonu tek başına TT/D hasarını azaltmak ve NF-κB ve MAPK'lerin aktivasyonunu inhibe etmek için yetersiz olabilir.

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Cite This Article

Kocakayaa, E., Dengiz, G. Ö., Yılmaz, Z., Ferah, M. A., Gülle, K. (2026). Is infliximab protective in testicular torsion/detorsion injury? NF-κB and MAPKs pathway (ERK1/2, JNK, p38 MAPK). Batı Karadeniz Tıp Dergisi, Cilt: 10 Sayı: 2, 289–299. https://doi.org/10.29058/mjwbs.1878407

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