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Effects of infliximab on testicular torsion/detorsion injury in rats

Year 2024, Volume: 49 Issue: 4, 925 - 934, 30.12.2024
https://doi.org/10.17826/cumj.1529709

Abstract

Purpose: This study aimed to investigate whether infliximab (INF), Tumor necrosis factor-alpha (TNF-α) monoclonal antibody, has a protective effect on experimental testiküler torsiyon/detorsiyon (TT/D) injury and whether apoptotic pathways contribute to this possible effect.
Materials and Methods: 42 male Wistar albino rats were randomly divided into three equal main groups: Sham, torsion/detorsion (T/D), and INF+T/D. Each group was then divided into two subgroups with detorsion periods of 24 hours (n =7) and 65 days (n=7). The right testes of anesthetized rats were rotated 720° clockwise for 3 hours to induce torsion. INF (ip, 5 mg/kg) was administered to the rats in the INF+T/D group 10 minutes before detorsion, while saline was administered to the rats in the other groups. At 24 hours after detorsion, the histopathological injury was evaluated by Johnsen scoring and caspase activities by immunohistochemical staining.
Results: Mean testis and cauda epididymis weights, sperm count, and Johnsen score were significantly lower in the T/D group than in the sham group. In addition, marked immunostaining of caspase-3, caspase-8, and caspase-9 was observed in spermatocytes and spermatids in the T/D group. INF administration did not prevent a decrease in testicular (0.80±0.132) and epididymal (0.121±0.247) weights, sperm count (2.0 ± 1.67 x106), or Johnsen score (8.70 ± 0.594). for caspases in spermatogenic cells.
Conclusion: In TT/D injury, INF treatment did not reduce apoptosis and testicular atrophy and did not increase sperm count. TNF-α blockage did not show a protective effect on rat TT/D injury.

Project Number

BEU BAP-2013-43341027-01

References

  • Ringdahl E, Teague L. Testicular torsion. Am Fam Physician. 2006;74:1739-43.
  • Almarzouq D, Al-Maghrebi M. NADPH Oxidase-Mediated Testicular Oxidative Imbalance Regulates the TXNIP/NLRP3 Inflammasome Axis Activation after Ischemia Reperfusion Injury. Antioxidants. 2023;12:145.
  • Al-Maghrebi M, Renno WM, Al-Somali HF, Botras MS, Qadhi IN. Lutein modulates transcription dysregulation of adhesion molecules and spermatogenesis transcription factors induced by testicular ischemia reperfusion injury: it could be SAFE. Naunyn Schmiedebergs Arch Pharmacol. 2016;389:539-51.
  • Al-Maghrebi M, Renno WM. The tACE/angiotensin (1-7)/mas axis protects against testicular ischemia reperfusion injury. Urology. 2016;94:312.e1-8.
  • Şahin Y, Üstüner E, Tutun H, Yildirim E, Eroğlu O, Kurtdede E et al. Effects of edaravone on testicular torsion-detorsion injury in rats. Andrology. 2024. doi: 10.1111/andr.13628.
  • Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta. 2013;1833:3448-59.
  • Belhan S, Yıldırım S, Karasu A, Kömüroğlu AU, Özdek U. Investigation of the protective role of chrysin within the framework of oxidative and inflammatory markers in experimental testicular ischaemia/reperfusion injury in rats. Andrologia. 2020;52:e13714.
  • Cayli S, Ocakli S, Senel U, Eyerci N, Delibasi T. Role of p97/Valosin-containing protein (VCP) and Jab1/CSN5 in testicular ischaemia-reperfusion injury. J Mol Histol. 2016;47:91-100.
  • Kim HJ, Lee JW, Hwang BR, Lee YA, Kim JI, Cho YJ, et al. Protective effect of pterostilbene on testicular ischemia/reperfusion injury in rats. J Pediatr Surg. 2016;51:1192–6.
  • Kocaman OH, Günendi T, Dörterler ME, Koyuncu I, Çelik H, Yumuşak N et al. Protective effect of osthole on testicular ischemia/reperfusion injury in rats. Ulus Travma Acil Cerrahi Derg. 2022;28:563-9.
  • Theas MS, Rival C, Jarazo-Dietrich S, Jacobo P, Guazzone VA, Lustig L. Tumour necrosis factor-alpha released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis. Hum Reprod. 2008;23:1865–72.
  • Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-79.
  • Kölükçü E, Atılgan D, Uluocak N, Deresoy FA, Katar M, Unsal V. Milrinone ameliorates ischaemia-reperfusion injury in experimental testicular torsion/detorsion rat model. Andrologia. 2021;53:e14128.
  • Xu LZ, He KX, Ning JZ, Cheng F. Oleuropein attenuates testicular ischemia-reperfusion by inhibiting apoptosis and inflammation. Tissue Cell. 2022;78:101876.
  • Mitoma H, Horiuchi T, Tsukamoto H, Ueda N. Molecular mechanisms of action of anti-TNF-α agents - Comparison among therapeutic TNF-α antagonists. Cytokine. 2018;101:56-63.
  • Mahmoud MF, El Shazly SM, Barakat W. Inhibition of TNF-α protects against hepatic ischemia-reperfusion injury in rats via NF-κB dependent pathway. Naunyn Schmiedebergs Arch Pharmacol. 2012;385:465-71.
  • Tasdemir C, Tasdemir S, Vardi N, Ates B, Parlakpinar H, Kati B et al. Protective effect of infliximab on ischemia/reperfusion-induced damage in rat kidney. Ren Fail. 2012;34:1144-9.
  • Guven C, Borcek AO, Cemil B, Kurt G, Yildirim Z, Ucankus NL et al. Neuroprotective effects of infliximab in experimental spinal cord ischemic injury. J Clin Neurosci. 2010;17:1563-7.
  • Livia C, Inglis S, Crespo-Diaz R, Rizzo S, Mahlberg R, Bagwell M et al. Infliximab Limits Injury in Myocardial Infarction. J Am Heart Assoc. 2024;13:e032172.
  • Yang Q, Zheng FP, Zhan YS, Tao J, Tan SW, Liu HL et al. Tumor necrosis factor-alpha mediates JNK activation response to intestinal ischemia-reperfusion injury. World J Gastroenterol. 2013;19:4925-34.
  • Hassan SM, Mohammed MH, Jawad MJ, Abbas AN. Use of infliximab to attenuate cerebral apoptosis induced by cerebral ischemia/reperfusion in male rats. Wiad Lek. 2023;76:326-331.
  • Turner TT, Tung KS, Tomomasa H, Wilson LW. Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol Reprod. 1997;57:1267-74.
  • Aly HAA, Domènech O, Banjar ZM. Effect of nonylphenol on male reproduction: analysis of rat epididymal biochemical markers and antioxidant defense enzymes. Toxicol Appl Pharmacol. 2012;261:134-41.
  • Johnsen SG. Testicular biopsy score count--a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones. 1970;1:2-25.
  • Kurcer Z, Oguz E, Ozbilge H, Baba F, Aksoy N, Celik N. Effect of melatonin on testicular ischemia/reperfusion injury in rats: is this effect related to the proinflammatory cytokines? Fertil Steril. 2008;89:1468-73.
  • Dasdag S, Akdag MZ, Ulukaya E, Uzunlar AK, Yegin D. Mobile phone exposure does not induce apoptosis on spermatogenesis in rats. Arch Med Res. 2008;39:40-4.
  • Celik M, Aydin P, Civelek MS, Akgun N, Karakoy Z, Ozcelik C et al. Avanafil mitigates testicular ischemia/reperfusion injury via NLRP3 pathway modulation in rats. Reprod Sci. 2024;31:3391-99.
  • Afolabi O, Alabi B, Omobowale T, Oluranti O, Iwalewa O. Cysteamine mitigates torsion/detorsion-induced reperfusion injury via inhibition of apoptosis, oxidative stress and inflammatory responses in experimental rat model. Andrologia. 2022;54:e14243.
  • de Oliveira SA, Cerri PS, Sasso-Cerri E. Impaired macrophages and failure of steroidogenesis and spermatogenesis in rat testes with cytokines deficiency induced by diacerein. Histochem Cell Biol. 2021;156:561-81.
  • Suh JH, Gong EY, Hong CY, Park E, Ahn RS, Park KS et al. Reduced testicular steroidogenesis in tumor necrosis factor-alpha knockout mice. J Steroid Biochem Mol Biol. 2008;112:117-21.
  • Lysiak JJ. The role of tumor necrosis factor-alpha and interleukin-1 in the mammalian testis and their involvement in testicular torsion and autoimmune orchitis. Reprod Biol Endocrinol. 2004;2:1-9.
  • Fischer R, Kontermann RE, Pfizenmaier K. Selective targeting of TNF receptors as a novel therapeutic approach. Front Cell Dev Biol. 2020;8:401.
  • Suominen JS, Wang Y, Kaipia A, Toppari J. Tumor necrosis factor-alpha (TNF-alpha) promotes cell survival during spermatogenesis, and this effect can be blocked by infliximab, a TNF-alpha antagonist. Eur J Endocrinol. 2004;151:629-40.
  • Pentikäinen V, Erkkilä K, Suomalainen L, Otalo M, Pentikäinen MO, Parvinen M et al. TNFalpha down-regulates the Fas ligand and inhibits germ cell apoptosis in the human testis. J Clin Endocrinol Metab. 2001;86:4480-8.
  • Lysiak JJ, Turner SD, Turner TT. Molecular pathway of germ cell apoptosis following ischemia/reperfusion of the rat testis. Biol Reprod. 2000;63:1465-72.
  • Zvizdic Z, Aganovic A, Milisic E, Jonuzi A, Zvizdic D, Vranic S. Duration of symptoms is the only predictor of testicular salvage following testicular torsion in children: A case-control study. Am J Emerg Med. 2021;41:197-200.
  • Wei SM, Yan ZZ, Zhou J. Beneficial effect of taurine on testicular ischemia-reperfusion injury in rats. Urology. 2007;70: 1237-42.
  • Zhang Y, Lv Y, Liu YJ, Hu HJ, Meng XE, Li MX et al. Hyperbaric oxygen therapy in rats attenuates ischemia-reperfusion testicular injury through blockade of oxidative stress, suppression of inflammation, and reduction of nitric oxide formation. Urology. 2013;82: 489.e9-.e15.
  • Yapanoglu T, Aksoy Y, Gursan N, Ozbey I, Ziypak T, Calik M. Antiapoptotic effects of dehydroepiandrosterone on testicular torsion/detorsion in rats. Andrologia. 2008;40:38-43.
  • Wong CH, Cheng CY. Mitogen-activated protein kinases, adherens junction dynamics, and spermatogenesis: a review of recent data. Dev Biol. 2005;286:1-15.
  • Micu MC, Micu R, Surd S, Gîrlovanu M, Bolboacă SD, Ostensen M. TNF-α inhibitors do not impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment. Rheumatol Oxf Engl. 2014;53:1250-5

İnfliximabın sıçanlarda testis torsiyon/detorsiyon hasarı üzerindeki etkileri

Year 2024, Volume: 49 Issue: 4, 925 - 934, 30.12.2024
https://doi.org/10.17826/cumj.1529709

Abstract

Amaç: Bu çalışmanın amacı, bir TNF-α monoklonal antikoru olan infliksimabın (INF) deneysel testiküler torsiyon/detorsiyon (TT/D) hasarı üzerinde koruyucu etkileri olup olmadığını ve bu olası etkide apoptotik yolakların katkısının olup olmadığını araştırmaktır.
Gereç ve Yöntem: 42 erkek Wistar albino sıçan rastgele eşit üç ana gruba ayrıldı: Sham, torsiyon/detorsiyon(T/D) ve INF+T/D. Her bir grup sonrasında detorsiyon süresi 24 saat (n=7) ve 65 gün (n=7) olan ikişer alt gruba ayrıldı. Anesteziye sıçanların sağ testisleri 3 saat boyunca saat yönünde 720° döndürülerek torsiyon oluşturuldu. INF+T/D grubundaki sıçanlara detorsiyondan 10 dakika önce INF (ip, 5 mg/kg) uygulanırken, diğer gruplardaki sıçanlara salin uygulandı. Detorsiyonun 24. saatinde, histopatolojik hasar Johnsen skorlaması ve kaspaz aktiviteleri immünohistokimyasal boyama ile değerlendirildi.
Bulgular: T/D grubunda ortalama testis ve kauda epididim ağırlıkları, sperm miktarı ve Johnsen skoru sham grubuna göre anlamlı derecede düşüktü. Ek olarak, spermatositlerde ve spermatidlerde kaspaz-3, kaspaz-8 ve kaspaz-9'un belirgin immün boyanması gözlendi. INF, testis (0.80±0.132) ve kauda epididim (0.121±0.247) ağırlıklarındaki, sperm miktarı (2.0 ± 1.67 x106) ve Johnsen skorundaki (8.70 ± 0.594) azalmayı önlemedi.
Sonuç: TT/D hasarında INF tedavisi apoptozu, testiküler atrofiyi azaltmadı ve sperm sayısını artırmadı. Sonuç olarak, TNF-α blokajı sıçan TT/D hasarı üzerinde koruyucu bir etki göstermemiştir.

Project Number

BEU BAP-2013-43341027-01

References

  • Ringdahl E, Teague L. Testicular torsion. Am Fam Physician. 2006;74:1739-43.
  • Almarzouq D, Al-Maghrebi M. NADPH Oxidase-Mediated Testicular Oxidative Imbalance Regulates the TXNIP/NLRP3 Inflammasome Axis Activation after Ischemia Reperfusion Injury. Antioxidants. 2023;12:145.
  • Al-Maghrebi M, Renno WM, Al-Somali HF, Botras MS, Qadhi IN. Lutein modulates transcription dysregulation of adhesion molecules and spermatogenesis transcription factors induced by testicular ischemia reperfusion injury: it could be SAFE. Naunyn Schmiedebergs Arch Pharmacol. 2016;389:539-51.
  • Al-Maghrebi M, Renno WM. The tACE/angiotensin (1-7)/mas axis protects against testicular ischemia reperfusion injury. Urology. 2016;94:312.e1-8.
  • Şahin Y, Üstüner E, Tutun H, Yildirim E, Eroğlu O, Kurtdede E et al. Effects of edaravone on testicular torsion-detorsion injury in rats. Andrology. 2024. doi: 10.1111/andr.13628.
  • Nikoletopoulou V, Markaki M, Palikaras K, Tavernarakis N. Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta. 2013;1833:3448-59.
  • Belhan S, Yıldırım S, Karasu A, Kömüroğlu AU, Özdek U. Investigation of the protective role of chrysin within the framework of oxidative and inflammatory markers in experimental testicular ischaemia/reperfusion injury in rats. Andrologia. 2020;52:e13714.
  • Cayli S, Ocakli S, Senel U, Eyerci N, Delibasi T. Role of p97/Valosin-containing protein (VCP) and Jab1/CSN5 in testicular ischaemia-reperfusion injury. J Mol Histol. 2016;47:91-100.
  • Kim HJ, Lee JW, Hwang BR, Lee YA, Kim JI, Cho YJ, et al. Protective effect of pterostilbene on testicular ischemia/reperfusion injury in rats. J Pediatr Surg. 2016;51:1192–6.
  • Kocaman OH, Günendi T, Dörterler ME, Koyuncu I, Çelik H, Yumuşak N et al. Protective effect of osthole on testicular ischemia/reperfusion injury in rats. Ulus Travma Acil Cerrahi Derg. 2022;28:563-9.
  • Theas MS, Rival C, Jarazo-Dietrich S, Jacobo P, Guazzone VA, Lustig L. Tumour necrosis factor-alpha released by testicular macrophages induces apoptosis of germ cells in autoimmune orchitis. Hum Reprod. 2008;23:1865–72.
  • Tracey D, Klareskog L, Sasso EH, Salfeld JG, Tak PP. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol Ther. 2008;117:244-79.
  • Kölükçü E, Atılgan D, Uluocak N, Deresoy FA, Katar M, Unsal V. Milrinone ameliorates ischaemia-reperfusion injury in experimental testicular torsion/detorsion rat model. Andrologia. 2021;53:e14128.
  • Xu LZ, He KX, Ning JZ, Cheng F. Oleuropein attenuates testicular ischemia-reperfusion by inhibiting apoptosis and inflammation. Tissue Cell. 2022;78:101876.
  • Mitoma H, Horiuchi T, Tsukamoto H, Ueda N. Molecular mechanisms of action of anti-TNF-α agents - Comparison among therapeutic TNF-α antagonists. Cytokine. 2018;101:56-63.
  • Mahmoud MF, El Shazly SM, Barakat W. Inhibition of TNF-α protects against hepatic ischemia-reperfusion injury in rats via NF-κB dependent pathway. Naunyn Schmiedebergs Arch Pharmacol. 2012;385:465-71.
  • Tasdemir C, Tasdemir S, Vardi N, Ates B, Parlakpinar H, Kati B et al. Protective effect of infliximab on ischemia/reperfusion-induced damage in rat kidney. Ren Fail. 2012;34:1144-9.
  • Guven C, Borcek AO, Cemil B, Kurt G, Yildirim Z, Ucankus NL et al. Neuroprotective effects of infliximab in experimental spinal cord ischemic injury. J Clin Neurosci. 2010;17:1563-7.
  • Livia C, Inglis S, Crespo-Diaz R, Rizzo S, Mahlberg R, Bagwell M et al. Infliximab Limits Injury in Myocardial Infarction. J Am Heart Assoc. 2024;13:e032172.
  • Yang Q, Zheng FP, Zhan YS, Tao J, Tan SW, Liu HL et al. Tumor necrosis factor-alpha mediates JNK activation response to intestinal ischemia-reperfusion injury. World J Gastroenterol. 2013;19:4925-34.
  • Hassan SM, Mohammed MH, Jawad MJ, Abbas AN. Use of infliximab to attenuate cerebral apoptosis induced by cerebral ischemia/reperfusion in male rats. Wiad Lek. 2023;76:326-331.
  • Turner TT, Tung KS, Tomomasa H, Wilson LW. Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol Reprod. 1997;57:1267-74.
  • Aly HAA, Domènech O, Banjar ZM. Effect of nonylphenol on male reproduction: analysis of rat epididymal biochemical markers and antioxidant defense enzymes. Toxicol Appl Pharmacol. 2012;261:134-41.
  • Johnsen SG. Testicular biopsy score count--a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones. 1970;1:2-25.
  • Kurcer Z, Oguz E, Ozbilge H, Baba F, Aksoy N, Celik N. Effect of melatonin on testicular ischemia/reperfusion injury in rats: is this effect related to the proinflammatory cytokines? Fertil Steril. 2008;89:1468-73.
  • Dasdag S, Akdag MZ, Ulukaya E, Uzunlar AK, Yegin D. Mobile phone exposure does not induce apoptosis on spermatogenesis in rats. Arch Med Res. 2008;39:40-4.
  • Celik M, Aydin P, Civelek MS, Akgun N, Karakoy Z, Ozcelik C et al. Avanafil mitigates testicular ischemia/reperfusion injury via NLRP3 pathway modulation in rats. Reprod Sci. 2024;31:3391-99.
  • Afolabi O, Alabi B, Omobowale T, Oluranti O, Iwalewa O. Cysteamine mitigates torsion/detorsion-induced reperfusion injury via inhibition of apoptosis, oxidative stress and inflammatory responses in experimental rat model. Andrologia. 2022;54:e14243.
  • de Oliveira SA, Cerri PS, Sasso-Cerri E. Impaired macrophages and failure of steroidogenesis and spermatogenesis in rat testes with cytokines deficiency induced by diacerein. Histochem Cell Biol. 2021;156:561-81.
  • Suh JH, Gong EY, Hong CY, Park E, Ahn RS, Park KS et al. Reduced testicular steroidogenesis in tumor necrosis factor-alpha knockout mice. J Steroid Biochem Mol Biol. 2008;112:117-21.
  • Lysiak JJ. The role of tumor necrosis factor-alpha and interleukin-1 in the mammalian testis and their involvement in testicular torsion and autoimmune orchitis. Reprod Biol Endocrinol. 2004;2:1-9.
  • Fischer R, Kontermann RE, Pfizenmaier K. Selective targeting of TNF receptors as a novel therapeutic approach. Front Cell Dev Biol. 2020;8:401.
  • Suominen JS, Wang Y, Kaipia A, Toppari J. Tumor necrosis factor-alpha (TNF-alpha) promotes cell survival during spermatogenesis, and this effect can be blocked by infliximab, a TNF-alpha antagonist. Eur J Endocrinol. 2004;151:629-40.
  • Pentikäinen V, Erkkilä K, Suomalainen L, Otalo M, Pentikäinen MO, Parvinen M et al. TNFalpha down-regulates the Fas ligand and inhibits germ cell apoptosis in the human testis. J Clin Endocrinol Metab. 2001;86:4480-8.
  • Lysiak JJ, Turner SD, Turner TT. Molecular pathway of germ cell apoptosis following ischemia/reperfusion of the rat testis. Biol Reprod. 2000;63:1465-72.
  • Zvizdic Z, Aganovic A, Milisic E, Jonuzi A, Zvizdic D, Vranic S. Duration of symptoms is the only predictor of testicular salvage following testicular torsion in children: A case-control study. Am J Emerg Med. 2021;41:197-200.
  • Wei SM, Yan ZZ, Zhou J. Beneficial effect of taurine on testicular ischemia-reperfusion injury in rats. Urology. 2007;70: 1237-42.
  • Zhang Y, Lv Y, Liu YJ, Hu HJ, Meng XE, Li MX et al. Hyperbaric oxygen therapy in rats attenuates ischemia-reperfusion testicular injury through blockade of oxidative stress, suppression of inflammation, and reduction of nitric oxide formation. Urology. 2013;82: 489.e9-.e15.
  • Yapanoglu T, Aksoy Y, Gursan N, Ozbey I, Ziypak T, Calik M. Antiapoptotic effects of dehydroepiandrosterone on testicular torsion/detorsion in rats. Andrologia. 2008;40:38-43.
  • Wong CH, Cheng CY. Mitogen-activated protein kinases, adherens junction dynamics, and spermatogenesis: a review of recent data. Dev Biol. 2005;286:1-15.
  • Micu MC, Micu R, Surd S, Gîrlovanu M, Bolboacă SD, Ostensen M. TNF-α inhibitors do not impair sperm quality in males with ankylosing spondylitis after short-term or long-term treatment. Rheumatol Oxf Engl. 2014;53:1250-5
There are 41 citations in total.

Details

Primary Language English
Subjects Urology
Journal Section Research
Authors

Semiral Albayrak Semalar 0000-0003-2663-1831

Zehra Yılmaz 0000-0002-9523-7718

Günnur Özbakış Dengiz 0000-0003-1117-3575

Kanat Gülle 0000-0002-6337-8962

Meryem Akpolat Ferah 0000-0002-3419-1728

Murat Can 0000-0002-1539-3973

Berrak Guven 0000-0003-4073-3164

Project Number BEU BAP-2013-43341027-01
Publication Date December 30, 2024
Submission Date August 8, 2024
Acceptance Date November 17, 2024
Published in Issue Year 2024 Volume: 49 Issue: 4

Cite

MLA Albayrak Semalar, Semiral et al. “Effects of Infliximab on Testicular torsion/Detorsion Injury in Rats”. Cukurova Medical Journal, vol. 49, no. 4, 2024, pp. 925-34, doi:10.17826/cumj.1529709.