{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T13:28:07Z","timestamp":1787232487559,"version":"build-2736575974"},"reference-count":35,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"F\u0131rat University Scientific Research Projects Coordination Unit","award":["TF.19.07"],"award-info":[{"award-number":["TF.19.07"]}]},{"name":"F\u0131rat University Scientific Research Projects Coordination Unit","award":["TF.26.55."],"award-info":[{"award-number":["TF.26.55."]}]},{"award":["TF.19.07"],"award-info":[{"award-number":["TF.19.07"]}],"id":[{"id":"https:\/\/ror.org\/05teb7b63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["TF.26.55."],"award-info":[{"award-number":["TF.26.55."]}],"id":[{"id":"https:\/\/ror.org\/05teb7b63","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Testicular torsion is a urological emergency that causes ischemia\u2013reperfusion (I\/R) injury and may result in irreversible germ cell loss and impaired fertility. Oxidative stress, inflammation, and apoptotic pathways play central roles in its pathogenesis. Transient Receptor Potential Melastatin-7 (TRPM7), a bifunctional ion channel\/kinase, has recently been implicated in I\/R-related cellular injury. Iloprost, a prostacyclin analogue with vasodilatory and antioxidant properties, may offer protective effects; however, its impact on TRPM7-mediated pathways in testicular I\/R injury remains unclear. This study aimed to investigate the effects of iloprost on oxidative stress, apoptosis, and TRPM7 expression in an experimental testicular torsion\u2013detorsion model. Thirty-five male Sprague Dawley rats were randomized into five groups: control, sham, iloprost, torsion\u2013detorsion (T\/D), and T\/D + iloprost. After 60 min of torsion and subsequent detorsion, iloprost (2 \u00b5g\/kg, intraperitoneal) was administered in the treatment group. Testicular tissues and serum samples were analyzed after 48 h. Histopathology (H&amp;E), apoptosis (TUNEL assay), TRPM7 immunohistochemistry and mRNA expression (RT-qPCR), and serum total antioxidant status (TAS) and total oxidant status (TOS) were evaluated. Torsion\u2013detorsion significantly increased TOS levels, apoptotic cell ratio (ACR), TRPM7 expression, and Bax mRNA expression, while reducing TAS levels (p &lt; 0.05). Iloprost administration significantly improved oxidative stress parameters, restoring TAS and reducing TOS compared with the untreated T\/D group. However, it did not significantly reduce histopathological damage, ACR, TRPM7 expression, or Bax mRNA expression. Bcl-2 expression remained largely unchanged across groups. Iloprost improved systemic oxidative status in testicular I\/R injury but did not significantly attenuate TRPM7 expression, apoptotic changes, or structural damage under the experimental conditions used. The concurrent increase in TRPM7 expression and apoptotic indices following torsion\u2013detorsion suggests an association between these alterations; however, the present study does not establish a causal relationship between TRPM7 and apoptosis. As TRPM7 activity was not directly assessed or experimentally manipulated, further studies involving TRPM7 inhibition or genetic silencing are required to determine its mechanistic role in testicular I\/R-induced apoptosis.<\/jats:p>","DOI":"10.3390\/ijms27167454","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:57:53Z","timestamp":1787230673000},"page":"7454","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Iloprost on TRPM7-Mediated Apoptosis and Oxidative Stress in an Experimental Testicular Torsion\u2013Detorsion Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8880-4932","authenticated-orcid":false,"given":"Nalan","family":"Kaya Tektemur","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazi\u011f 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aysenur","family":"Bilgetay Unlu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazi\u011f 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-3660","authenticated-orcid":false,"given":"Merve","family":"Kavak Balgetir","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Elazig Fethi Sekin City Hospital, Elazi\u011f 23280, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2476-0413","authenticated-orcid":false,"given":"Ahmet","family":"Tektemur","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, Firat University, Elazi\u011f 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6874-3669","authenticated-orcid":false,"given":"Gonca","family":"Ozan Kocamuftuoglu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Burdur Mehmet Akif Ersoy University, Burdur 15030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0559-8932","authenticated-orcid":false,"given":"Ramazan Fazil","family":"Akkoc","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Kutahya Health Sciences University, K\u00fctahya 43020, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4962-387X","authenticated-orcid":false,"given":"Osman Fatih","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Pathology Laboratory Techniques, Faculty of Medicine, Mus Alparslan University, Mu\u015f 49250, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esra","family":"Aydemir","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazi\u011f 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9874-3838","authenticated-orcid":false,"given":"Tuncay","family":"Kuloglu","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Firat University, Elazi\u011f 23119, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1111\/andr.13418","article-title":"Testicular torsion in vivo models: Mechanisms and treatments","volume":"11","author":"Minas","year":"2023","journal-title":"Andrology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e27760","DOI":"10.1016\/j.heliyon.2024.e27760","article-title":"Pathophysiology and management of testicular ischemia\/reperfusion injury: Lessons from animal models","volume":"10","author":"Akhigbe","year":"2024","journal-title":"Heliyon"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"784","DOI":"10.5534\/wjmh.250214","article-title":"Molecular Mechanisms of Testis Damage and Target Drug Development in the Ischemic-Reperfusion Injury of Acute Testicular Torsion: A Pediatric Urological Perspective","volume":"43","author":"Chung","year":"2025","journal-title":"World J. Men\u2019s Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"32","DOI":"10.26641\/1997-9665.2024.1.32-40","article-title":"Pathomorphological and immunohistochemical characteristics of the testicle in children with critical ischemia during acute torsion","volume":"18","author":"Volos","year":"2024","journal-title":"Morphologia"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ajike, R.A., Ajayi, A.F., Oyekunle, O.S., Saka, W.A., Hammed, S.O., Adedeji, O.J., Ogunleye, O.D., Hezekiah, O.S., Olayinka-Akinpelu, O.V., and Alabi, B.A. (2025). Potential therapeutic targets in the prevention of testicular ischemia-reperfusion injury. Front. Reprod. Health, 7.","DOI":"10.3389\/frph.2025.1706914"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1186\/s13287-021-02439-x","article-title":"Combined melatonin-adipose derived mesenchymal stem cells therapy effectively protected the testis from testicular torsion-induced ischemia-reperfusion injury","volume":"12","author":"Chen","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"9043806","DOI":"10.1155\/2020\/9043806","article-title":"Sesamol Protects Testis from Ischemia-Reperfusion Injury through Scavenging Reactive Oxygen Species and Upregulating CREM\u03c4 Expression","volume":"2020","author":"Wei","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1111\/iju.13110","article-title":"Testicular torsion\u2013detorsion and potential therapeutic treatments: A possible role for ischemic postconditioning","volume":"23","author":"Shimizu","year":"2016","journal-title":"Int. J. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Almarzouq, D., and Al-Maghrebi, M. (2023). NADPH Oxidase-Mediated Testicular Oxidative Imbalance Regulates the TXNIP\/NLRP3 Inflammasome Axis Activation after Ischemia Reperfusion Injury. Antioxidants, 12.","DOI":"10.3390\/antiox12010145"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1603469","DOI":"10.1155\/2022\/1603469","article-title":"Baicalein Alleviates Testicular Ischemia-Reperfusion Injury in a Rat Model of Testicular Torsion-Detorsion","volume":"2022","author":"Wei","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.1097\/01.ju.0000144203.30718.19","article-title":"The molecular pathology of experimental testicular torsion suggests adjunct therapy to surgical repair","volume":"172","author":"Turner","year":"2004","journal-title":"J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1016\/j.sjbs.2020.04.024","article-title":"Inhibition of NADPH oxidase alleviates germ cell apoptosis and ER stress during testicular ischemia reperfusion injury","volume":"27","author":"Khashab","year":"2020","journal-title":"Saudi J. Biol. Sci."},{"key":"ref_13","first-page":"665","article-title":"Protective effects of Mito-TEMPO on ischemia-reperfusion injury in a mouse testicular torsion and detorsion model","volume":"15","author":"Mostahsan","year":"2024","journal-title":"Vet. Res. Forum"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Davoodi, F., Taheri, S., Raisi, A., Rajabzadeh, A., Zakian, A., Hablolvarid, M.H., and Ahmadvand, H. (2021). Leech therapy (Hirudo medicinalis) attenuates testicular damages induced by testicular ischemia\/reperfusion in an animal model. BMC Veter-Res., 17.","DOI":"10.1186\/s12917-021-02951-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1113\/JP273709","article-title":"Role of TRPM7 in cerebral ischaemia and hypoxia","volume":"595","author":"Sun","year":"2017","journal-title":"J. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/S0092-8674(03)01017-1","article-title":"A Key Role for TRPM7 Channels in Anoxic Neuronal Death","volume":"115","author":"Aarts","year":"2003","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1038\/s41598-018-22852-2","article-title":"TRPM7 in CHBP-induced renoprotection upon ischemia reperfusion-related injury","volume":"8","author":"Liu","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Piciu, F., Balas, M., Badea, M.A., and Cucu, D. (2023). TRP Channels in Tumoral Processes Mediated by Oxidative Stress and Inflammation. Antioxidants, 12.","DOI":"10.20944\/preprints202305.1357.v1"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"G\u0105secka, A., Banaszkiewicz, M., Nieuwland, R., van der Pol, E., Hajji, N., Mutwil, H., Rogula, S., Rutkowska, W., Pluta, K., and Eyileten, C. (2021). Prostacyclin Analogues Inhibit Platelet Reactivity, Extracellular Vesicle Release and Thrombus Formation in Patients with Pulmonary Arterial Hypertension. J. Clin. Med., 10.","DOI":"10.3390\/jcm10051024"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/0886022X.2011.633446","article-title":"Affirmative Effects of Iloprost on Apoptosis during Ischemia\u2013Reperfusion Injury in Kidney as a Distant Organ","volume":"34","author":"Canacankatan","year":"2011","journal-title":"Ren. Fail."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.3906\/sag-1604-59","article-title":"The effects of iloprost and alprostadil on ischemia-reperfusion injury in preventing inflammation, tissue degeneration, and apoptosis in rat skeletal muscle","volume":"47","author":"Ovali","year":"2017","journal-title":"Turk. J. Med. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Ayad, B., Omolaoye, T.S., Louw, N., Ramsunder, Y., Skosana, B.T., Oyeipo, P.I., and Du Plessis, S.S. (2022). Oxidative Stress and Male Infertility: Evidence From a Research Perspective. Front. Reprod. Health, 4.","DOI":"10.3389\/frph.2022.822257"},{"key":"ref_23","first-page":"e14243","article-title":"Cysteamine mitigates torsion\/detorsion-induced reperfusion injury via inhibition of apoptosis, oxidative stress and inflammatory responses in experimental rat model","volume":"54","author":"Afolabi","year":"2021","journal-title":"Andrologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"45023","DOI":"10.1038\/s41598-025-29283-w","article-title":"HMG-CoA reductase inhibition preserves testicular function after torsion\/detorsion by modulating oxidative stress and AKT signaling","volume":"15","author":"Beker","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1080\/08941939.2021.1995540","article-title":"Astaxanthin Protects Testicular Tissue against Torsion\/Detorsion-Induced Injury via Suppressing Endoplasmic Reticulum Stress in Rats","volume":"35","author":"Demir","year":"2022","journal-title":"J. Investig. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.transproceed.2011.11.068","article-title":"Expression of Transient Receptor Potential Melastatin 7 Up-regulated in the Early Stage of Renal Ischemia-Reperfusion","volume":"44","author":"Meng","year":"2012","journal-title":"Transplant. Proc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s10151-011-0758-5","article-title":"The effects of iloprost on colonic anastomotic healing in rats","volume":"15","author":"Galanopoulos","year":"2011","journal-title":"Tech. Coloproctol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"889","DOI":"10.2165\/00003495-199243060-00008","article-title":"A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peripheral vascular disease, myocardial ischaemia and extracorporeal circulation procedures","volume":"43","author":"Grant","year":"1992","journal-title":"Drugs"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Faggioli, P.M., Mumoli, N., and Mazzone, A. (2021). Iloprost in COVID-19: The Rationale of Therapeutic Benefit. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.649499"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1124\/pr.111.004770","article-title":"Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn","volume":"64","author":"Majed","year":"2012","journal-title":"Pharmacol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1038\/s41392-023-01688-x","article-title":"Ischemia-reperfusion injury: Molecular mechanisms and therapeutic targets","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.jpedsurg.2007.12.063","article-title":"Ethyl pyruvate reduces germ cell-specific apoptosis and oxidative stress in rat model of testicular torsion\/detorsion","volume":"43","author":"Payabvash","year":"2008","journal-title":"J. Pediatr. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43.e1","DOI":"10.1016\/j.jpurol.2018.09.012","article-title":"Remote ischemic conditioning in a rat model of testicular torsion: Does it offer testicular protection?","volume":"15","author":"Mansour","year":"2019","journal-title":"J. Pediatr. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3233\/CH-200934","article-title":"Protective effect of inhibiting TRPM7 expression on hypoxia post-treatment H9C2 cardiomyocytes","volume":"77","author":"Yang","year":"2020","journal-title":"Clin. Hemorheol. Microcirc."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Sarmiento, A., Dur\u00e1n-D\u00edaz, I., Fond\u00f3n, I., Tom\u00e9, M., Bodineau, C., and Dur\u00e1n, R.V. (2022). A Method for Unsupervised Semi-Quantification of Inmunohistochemical Staining with Beta Divergences. Entropy, 24.","DOI":"10.3390\/e24040546"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7454\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T12:58:34Z","timestamp":1787230714000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7454"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,20]]},"references-count":35,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167454"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167454","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,20]]}}}