{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:06:24Z","timestamp":1787313984110,"version":"build-2736575974"},"reference-count":78,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"The Istanbul Medipol University BAP Commission","award":["2022\/32"],"award-info":[{"award-number":["2022\/32"]}]},{"DOI":"10.13039\/501100004412","name":"Turkish Academy of Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004412","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-29283-w","type":"journal-article","created":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T16:53:42Z","timestamp":1763830422000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HMG-CoA reductase inhibition preserves testicular function after torsion\/detorsion by modulating oxidative stress and AKT signaling"],"prefix":"10.1038","volume":"15","author":[{"given":"Berna","family":"Y\u0131ld\u0131r\u0131m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O\u011fuzhan","family":"Bayg\u00fcl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nursena","family":"\u015eeng\u00fcn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dcnsal Veli","family":"\u00dcst\u00fcnda\u011f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilay","family":"Ate\u015f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep","family":"Bal\u00e7\u0131kanl\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa \u00c7a\u011flar","family":"Beker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130lknur","family":"Keskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ertu\u011frul","family":"K\u0131l\u0131\u00e7","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"29283_CR1","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.urology.2017.11.034","volume":"114","author":"T Yecies","year":"2018","unstructured":"Yecies, T., Bandari, J., Schneck, F. & Cannon, G. Direction of rotation in testicular torsion and identification of predictors of testicular salvage. Urology 114, 163\u2013166 (2018).","journal-title":"Urology"},{"key":"29283_CR2","doi-asserted-by":"crossref","unstructured":"Korkes, F., Cabral, P. R., Alves, A., Savioli, C. D. M. & Pompeo, A. C. dos, M. L. L. Testicular torsion and weather conditions: analysis of 21,289 cases in Brazil. Int. Braz J Urol Off. J. Braz. Soc. Urol. 38, 222\u2013228; discussion 228\u2013229 (2012).","DOI":"10.1590\/S1677-55382012000200010"},{"key":"29283_CR3","doi-asserted-by":"publisher","DOI":"10.1111\/and.12969","author":"F Gevrek","year":"2018","unstructured":"Gevrek, F., Bi\u00e7er, \u00c7., Kara, M. & Erdemir, F. The ameliorative effects of Ginkgo Biloba on apoptosis, LH-R expression and sperm morphology anomaly in testicular torsion and detorsion. Andrologia https:\/\/doi.org\/10.1111\/and.12969 (2018). doi:10.1111\/and.12969.","journal-title":"Andrologia"},{"key":"29283_CR4","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.bbrc.2012.03.013","volume":"420","author":"M Al-Maghrebi","year":"2012","unstructured":"Al-Maghrebi, M., Renno, W. M. & Al-Ajmi, N. Epigallocatechin-3-gallate inhibits apoptosis and protects testicular seminiferous tubules from ischemia\/reperfusion-induced inflammation. Biochem. Biophys. Res. Commun. 420, 434\u2013439 (2012).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"29283_CR5","doi-asserted-by":"publisher","first-page":"152084","DOI":"10.1016\/j.aanat.2023.152084","volume":"249","author":"M Ramesh","year":"2023","unstructured":"Ramesh, M. et al. Protective effects of human amniotic membrane derived mesenchymal stem cells (hAMSCs) secreted factors on mouse spermatogenesis and sperm chromatin condensation following unilateral testicular torsion. Ann. Anat. Anat. Anz Off Organ. Anat. Ges. 249, 152084 (2023).","journal-title":"Ann. Anat. Anat. Anz Off Organ. Anat. Ges"},{"key":"29283_CR6","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.theriogenology.2020.01.002","volume":"144","author":"F Davoodi","year":"2020","unstructured":"Davoodi, F. et al. Investigating the sperm parameters, oxidative stress and histopathological effects of salvia miltiorrhiza hydroalcoholic extract in the prevention of testicular ischemia reperfusion damage in rats. Theriogenology 144, 98\u2013106 (2020).","journal-title":"Theriogenology"},{"key":"29283_CR7","doi-asserted-by":"crossref","unstructured":"O\u2019Flaherty, C., Scarlata, E., OXIDATIVE STRESS AND REPRODUCTIVE & FUNCTION. The protection of mammalian spermatozoa against oxidative stress. Reprod. Camb. Engl. 164, F67\u2013F78 (2022).","DOI":"10.1530\/REP-22-0200"},{"key":"29283_CR8","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1016\/j.fertnstert.2009.01.146","volume":"93","author":"Z Kurcer","year":"2010","unstructured":"Kurcer, Z., Hekimoglu, A., Aral, F., Baba, F. & Sahna, E. Effect of melatonin on epididymal sperm quality after testicular ischemia\/reperfusion in rats. Fertil. Steril. 93, 1545\u20131549 (2010).","journal-title":"Fertil. Steril."},{"key":"29283_CR9","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1095\/biolreprod.115.137646","volume":"94","author":"B Ozkosem","year":"2016","unstructured":"Ozkosem, B., Feinstein, S. I., Fisher, A. B. & O\u2019Flaherty, C. Absence of Peroxiredoxin 6 amplifies the effect of oxidant stress on mobility and SCSA\/CMA3 defined chromatin quality and impairs fertilizing ability of mouse spermatozoa. Biol. Reprod. 94, 68 (2016).","journal-title":"Biol. Reprod."},{"key":"29283_CR10","doi-asserted-by":"publisher","first-page":"e230024","DOI":"10.1530\/RAF-23-0024","volume":"4","author":"NB Takalani","year":"2023","unstructured":"Takalani, N. B. et al. Role of oxidative stress in male infertility. Reprod. Fertil. 4, e230024 (2023).","journal-title":"Reprod. Fertil."},{"key":"29283_CR11","doi-asserted-by":"publisher","first-page":"385","DOI":"10.5713\/ab.22.0325","volume":"36","author":"AY Qamar","year":"2023","unstructured":"Qamar, A. Y. et al. Role of antioxidants in fertility preservation of sperm \u2014 A narrative review. Anim. Biosci. 36, 385\u2013403 (2023).","journal-title":"Anim. Biosci."},{"key":"29283_CR12","doi-asserted-by":"publisher","first-page":"104594","DOI":"10.1016\/j.cryobiol.2023.104594","volume":"113","author":"MN Kolyada","year":"2023","unstructured":"Kolyada, M. N., Osipova, V. P. & Pimenov, Y. T. Oxidative stress and cryoresistance of sturgeon sperm: A review. Cryobiology 113, 104594 (2023).","journal-title":"Cryobiology"},{"key":"29283_CR13","doi-asserted-by":"publisher","first-page":"1520835","DOI":"10.3389\/fendo.2025.1520835","volume":"16","author":"Y Wang","year":"2025","unstructured":"Wang, Y., Fu, X. & Li, H. Mechanisms of oxidative stress-induced sperm dysfunction. Front. Endocrinol. 16, 1520835 (2025).","journal-title":"Front. Endocrinol."},{"key":"29283_CR14","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1089\/ars.2021.0241","volume":"37","author":"JC Ribeiro","year":"2022","unstructured":"Ribeiro, J. C. et al. Exploring the role of oxidative stress in sperm motility: A proteomic network approach. Antioxid. Redox Signal. 37, 501\u2013520 (2022).","journal-title":"Antioxid. Redox Signal."},{"key":"29283_CR15","doi-asserted-by":"publisher","first-page":"115","DOI":"10.5152\/eurasianjmed.2020.19229","volume":"52","author":"Z Sertkaya","year":"2020","unstructured":"Sertkaya, Z. et al. Protective effect of Udenafil against ischemia reperfusion injury due to testicular Torsion\/Detorsion in rat model. Eurasian J. Med. 52, 115\u2013119 (2020).","journal-title":"Eurasian J. Med."},{"key":"29283_CR16","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1590\/s1677-5538.ibju.2018.0200","volume":"44","author":"C Yildirim","year":"2018","unstructured":"Yildirim, C. et al. Protective effects of Tadalafil and Darbepoetin against ischemia - reperfusion injury in a rat testicular torsion model. Int. Braz J. Urol. Off J. Braz Soc. Urol. 44, 1005\u20131013 (2018).","journal-title":"Int. Braz J. Urol. Off J. Braz Soc. Urol."},{"key":"29283_CR17","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s40360-022-00601-6","volume":"23","author":"I Yazdani","year":"2022","unstructured":"Yazdani, I., Majdani, R., Ghasemnejad-Berenji, M. & Dehpour, A. R. Beneficial effects of cyclosporine A in combination with Nortriptyline on germ cell-specific apoptosis, oxidative stress and epididymal sperm qualities following testicular ischemia\/reperfusion in rats: a comparative study. BMC Pharmacol. Toxicol. 23, 59 (2022).","journal-title":"BMC Pharmacol. Toxicol."},{"key":"29283_CR18","doi-asserted-by":"publisher","first-page":"687585","DOI":"10.3389\/fcvm.2021.687585","volume":"8","author":"E Climent","year":"2021","unstructured":"Climent, E. & Benaiges, D. Pedro-Botet, J. Hydrophilic or lipophilic statins? Front. Cardiovasc. Med. 8, 687585 (2021).","journal-title":"Front. Cardiovasc. Med."},{"key":"29283_CR19","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1161\/01.STR.0000152273.24063.f7","volume":"36","author":"E Kilic","year":"2005","unstructured":"Kilic, E. et al. Aggravation of focal cerebral ischemia by tissue plasminogen activator is reversed by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor but does not depend on endothelial NO synthase. Stroke 36, 332\u2013336 (2005).","journal-title":"Stroke"},{"key":"29283_CR20","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.nbd.2005.04.002","volume":"20","author":"A Spudich","year":"2005","unstructured":"Spudich, A. et al. Aggravation of ischemic brain injury by prion protein deficiency: role of ERK-1\/-2 and STAT-1. Neurobiol. Dis. 20, 442\u2013449 (2005).","journal-title":"Neurobiol. Dis."},{"key":"29283_CR21","doi-asserted-by":"publisher","first-page":"422","DOI":"10.3389\/fncel.2014.00422","volume":"8","author":"E Kilic","year":"2014","unstructured":"Kilic, E. et al. HMG-CoA reductase Inhibition promotes neurological Recovery, Peri-Lesional tissue Remodeling, and contralesional pyramidal tract plasticity after focal cerebral ischemia. Front. Cell. Neurosci. 8, 422 (2014).","journal-title":"Front. Cell. Neurosci."},{"key":"29283_CR22","doi-asserted-by":"publisher","first-page":"282","DOI":"10.5853\/jos.2015.17.3.282","volume":"17","author":"KS Hong","year":"2015","unstructured":"Hong, K. S. & Lee, J. S. Statins in acute ischemic stroke: A systematic review. J. Stroke. 17, 282\u2013301 (2015).","journal-title":"J. Stroke"},{"key":"29283_CR23","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/79510","volume":"6","author":"Y Kureishi","year":"2000","unstructured":"Kureishi, Y. et al. The HMG-CoA reductase inhibitor Simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat. Med. 6, 1004\u20131010 (2000).","journal-title":"Nat. Med."},{"key":"29283_CR24","first-page":"2319","volume":"53","author":"GM Nitulescu","year":"2018","unstructured":"Nitulescu, G. M. et al. The Akt pathway in oncology therapy and beyond (Review). Int. J. Oncol. 53, 2319\u20132331 (2018).","journal-title":"Int. J. Oncol."},{"key":"29283_CR25","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1007\/s00204-023-03492-6","volume":"97","author":"CA German","year":"2023","unstructured":"German, C. A. & Liao, J. K. Understanding the molecular mechanisms of Statin pleiotropic effects. Arch. Toxicol. 97, 1529\u20131545 (2023).","journal-title":"Arch. Toxicol."},{"key":"29283_CR26","doi-asserted-by":"publisher","first-page":"1515","DOI":"10.1016\/j.cellsig.2011.05.004","volume":"23","author":"I Hers","year":"2011","unstructured":"Hers, I., Vincent, E. E. & Tavar\u00e9, J. M. Akt signalling in health and disease. Cell. Signal. 23, 1515\u20131527 (2011).","journal-title":"Cell. Signal."},{"key":"29283_CR27","doi-asserted-by":"publisher","first-page":"869","DOI":"10.3892\/ijo.2015.3306","volume":"48","author":"GM NITULESCU","year":"2015","unstructured":"NITULESCU, G. M. et al. Akt inhibitors in cancer treatment: the long journey from drug discovery to clinical use (Review). Int. J. Oncol. 48, 869\u2013885 (2015).","journal-title":"Int. J. Oncol."},{"key":"29283_CR28","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.redox.2017.04.006","volume":"12","author":"U Kilic","year":"2017","unstructured":"Kilic, U. et al. Particular phosphorylation of PI3K\/Akt on Thr308 via PDK-1 and PTEN mediates melatonin\u2019s neuroprotective activity after focal cerebral ischemia in mice. Redox Biol. 12, 657\u2013665 (2017).","journal-title":"Redox Biol."},{"key":"29283_CR29","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.3892\/etm.2021.10478","volume":"22","author":"Z Li","year":"2021","unstructured":"Li, Z., Cao, X., Xiao, L. & Zhou, R. Aloperine protects against cerebral ischemia\/reperfusion injury via activating the PI3K\/AKT signaling pathway in rats. Exp. Ther. Med. 22, 1045 (2021).","journal-title":"Exp. Ther. Med."},{"key":"29283_CR30","doi-asserted-by":"publisher","first-page":"1841","DOI":"10.1016\/j.bbamcr.2015.04.010","volume":"1853","author":"A Bonifacio","year":"2015","unstructured":"Bonifacio, A., Sanvee, G. M., Bouitbir, J. & Kr\u00e4henb\u00fchl, S. The AKT\/mTOR signaling pathway plays a key role in statin-induced myotoxicity. Biochim. Biophys. Acta. 1853, 1841\u20131849 (2015).","journal-title":"Biochim. Biophys. Acta"},{"key":"29283_CR31","unstructured":"Musorowegomo, D. Development toxicity effects of Atorvastatin and Rosuvastatin in mice. Masters thesis, University of Zimbabwe.(2016)."},{"key":"29283_CR32","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.neuroscience.2014.10.014","volume":"284","author":"FB Seker","year":"2015","unstructured":"Seker, F. B. et al. HMG-CoA reductase inhibitor Rosuvastatin improves abnormal brain electrical activity via mechanisms involving eNOS. Neuroscience 284, 349\u2013359 (2015).","journal-title":"Neuroscience"},{"key":"29283_CR33","first-page":"044","volume":"13","author":"S Sharma","year":"2021","unstructured":"Sharma, S. et al. Evaluation of the effect of Rosuvastatin and Fenofibrate alone and in combination on chronic unpredictable mild stress induced depression in Wistar rats. Open. Access. J. Neurol. Neurosurg. 13, 044\u2013056 (2021).","journal-title":"Open. Access. J. Neurol. Neurosurg."},{"key":"29283_CR34","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/S0735-1097(03)00926-4","volume":"42","author":"D Susic","year":"2003","unstructured":"Susic, D., Varagic, J., Ahn, J., Slama, M. & Frohlich, E. D. Beneficial pleiotropic vascular effects of Rosuvastatin in two hypertensive models. J. Am. Coll. Cardiol. 42, 1091\u20131097 (2003).","journal-title":"J. Am. Coll. Cardiol."},{"key":"29283_CR35","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1186\/2047-783X-15-11-461","volume":"15","author":"M Preusch","year":"2010","unstructured":"Preusch, M. et al. Rosuvastatin reduces Neointima formation in a rat model of balloon injury. Eur. J. Med. Res. 15, 461 (2010).","journal-title":"Eur. J. Med. Res."},{"key":"29283_CR36","first-page":"92","volume":"4","author":"\u00d6 Topda\u011f\u0131","year":"2019","unstructured":"Topda\u011f\u0131, \u00d6. et al. Higenamine decreases testicular damage injured by ischemia reperfusion: A biochemical study. Turk. J. Sci. 4, 92\u201399 (2019).","journal-title":"Turk. J. Sci."},{"key":"29283_CR37","first-page":"28","volume":"5","author":"\u00d6 Topda\u011f\u0131","year":"2020","unstructured":"Topda\u011f\u0131, \u00d6., Tanyeli, A., Ekinci, F., Eraslan, E. & G\u00fcler, M. C. Barbaloin attenuates oxidative testicular injury induced by ischemia reperfusion via antioxidant effects. Turk. J. Sci. 5, 28\u201333 (2020).","journal-title":"Turk. J. Sci."},{"key":"29283_CR38","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1095\/biolreprod65.3.718","volume":"65","author":"JJ Lysiak","year":"2001","unstructured":"Lysiak, J. J. et al. Essential role of neutrophils in germ cell-specific apoptosis following ischemia\/reperfusion injury of the mouse testis. Biol. Reprod. 65, 718\u2013725 (2001).","journal-title":"Biol. Reprod."},{"key":"29283_CR39","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.1097\/01.ju.0000144203.30718.19","volume":"172","author":"TT Turner","year":"2004","unstructured":"Turner, T. T., Bang, H. J. & Lysiak, J. L. The molecular pathology of experimental testicular torsion suggests adjunct therapy to surgical repair. J. Urol. 172, 2574\u20132578 (2004).","journal-title":"J. Urol."},{"key":"29283_CR40","doi-asserted-by":"crossref","unstructured":"Wei, S. M., Huang, Y. M. & Zhou, J. Probucol Reduces Testicular Torsion\/Detorsion-Induced Ischemia\/Reperfusion Injury in Rats. Oxid. Med. Cell. Longev.2017, 5424097 (2017).","DOI":"10.1155\/2017\/5424097"},{"key":"29283_CR41","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1186\/s12917-021-02951-5","volume":"17","author":"F Davoodi","year":"2021","unstructured":"Davoodi, F. et al. Leech therapy (Hirudo medicinalis) attenuates testicular damages induced by testicular ischemia\/reperfusion in an animal model. BMC Vet. Res. 17, 256 (2021).","journal-title":"BMC Vet. Res."},{"key":"29283_CR42","doi-asserted-by":"publisher","first-page":"75","DOI":"10.2164\/jandrol.107.004333","volume":"30","author":"O Varisli","year":"2009","unstructured":"Varisli, O., Uguz, C., Agca, C. & Agca, Y. Various physical stress factors on rat sperm motility, integrity of acrosome, and plasma membrane. J. Androl. 30, 75\u201386 (2009).","journal-title":"J. Androl."},{"key":"29283_CR43","doi-asserted-by":"publisher","first-page":"1368","DOI":"10.3390\/life11121368","volume":"11","author":"F Boitrelle","year":"2021","unstructured":"Boitrelle, F. et al. The sixth edition of the WHO manual for human semen analysis: A critical review and SWOT analysis. Life 11, 1368 (2021).","journal-title":"Life"},{"key":"29283_CR44","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/S0015-0282(16)59660-5","volume":"49","author":"TF Kruger","year":"1988","unstructured":"Kruger, T. F. et al. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil. Steril. 49, 112\u2013117 (1988).","journal-title":"Fertil. Steril."},{"key":"29283_CR45","doi-asserted-by":"publisher","first-page":"e13775","DOI":"10.1111\/and.13775","volume":"52","author":"E Ek\u015fi","year":"2020","unstructured":"Ek\u015fi, E. et al. Effects of myricetin on testicular torsion-detorsion injury in rats. Andrologia 52, e13775 (2020).","journal-title":"Andrologia"},{"key":"29283_CR46","first-page":"2","volume":"1","author":"SG Johnsen","year":"1970","unstructured":"Johnsen, S. G. Testicular biopsy score count\u2013a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones 1, 2\u201325 (1970).","journal-title":"Hormones"},{"key":"29283_CR47","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1002\/j.1939-4640.1986.tb00862.x","volume":"7","author":"MJ Cosentino","year":"1986","unstructured":"Cosentino, M. J., Nishida, M., Rabinowitz, R. & Cockett, A. T. Histopathology of prepubertal rat testes subjected to various durations of spermatic cord torsion. J. Androl. 7, 23\u201331 (1986).","journal-title":"J. Androl."},{"key":"29283_CR48","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.clinbiochem.2003.11.015","volume":"37","author":"O Erel","year":"2004","unstructured":"Erel, O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin. Biochem. 37, 277\u2013285 (2004).","journal-title":"Clin. Biochem."},{"key":"29283_CR49","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.clinbiochem.2005.08.008","volume":"38","author":"O Erel","year":"2005","unstructured":"Erel, O. A new automated colorimetric method for measuring total oxidant status. Clin. Biochem. 38, 1103\u20131111 (2005).","journal-title":"Clin. Biochem."},{"key":"29283_CR50","doi-asserted-by":"publisher","first-page":"30604","DOI":"10.18632\/oncotarget.5773","volume":"6","author":"MC Beker","year":"2015","unstructured":"Beker, M. C. et al. Effects of Normobaric oxygen and melatonin on reperfusion injury: role of cerebral microcirculation. Oncotarget 6, 30604\u201330614 (2015).","journal-title":"Oncotarget"},{"key":"29283_CR51","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1111\/andr.13418","volume":"11","author":"A Minas","year":"2023","unstructured":"Minas, A. et al. Testicular torsion in vivo models: mechanisms and treatments. Andrology 11, 1267\u20131285 (2023).","journal-title":"Andrology"},{"key":"29283_CR52","doi-asserted-by":"publisher","first-page":"111975","DOI":"10.1016\/j.biopha.2021.111975","volume":"142","author":"RE Akhigbe","year":"2021","unstructured":"Akhigbe, R. E. et al. Omega-3 fatty acid rescues ischaemia\/perfusion-induced testicular and sperm damage via modulation of lactate transport and Xanthine oxidase\/uric acid signaling. Biomed. Pharmacother Biomedecine Pharmacother. 142, 111975 (2021).","journal-title":"Biomed. Pharmacother Biomedecine Pharmacother"},{"key":"29283_CR53","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.ajem.2020.03.060","volume":"44","author":"A Jafari","year":"2021","unstructured":"Jafari, A., Ghasemnejad-Berenji, H., Nemati, M., Ghasemnejad-Berenji, M. & Topiramate A novel protective agent against ischemia reperfusion-induced oxidative injury after testicular torsion\/detorsion. Am. J. Emerg. Med. 44, 257\u2013261 (2021).","journal-title":"Am. J. Emerg. Med."},{"key":"29283_CR54","doi-asserted-by":"publisher","first-page":"1110572","DOI":"10.3389\/fendo.2023.1110572","volume":"14","author":"I Bhattacharya","year":"2023","unstructured":"Bhattacharya, I., Dey, S. & Banerjee, A. Revisiting the gonadotropic regulation of mammalian spermatogenesis: evolving lessons during the past decade. Front. Endocrinol. 14, 1110572 (2023).","journal-title":"Front. Endocrinol."},{"key":"29283_CR55","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1038\/s41390-023-02638-7","volume":"94","author":"H Katami","year":"2023","unstructured":"Katami, H. et al. Genetic and histopathological analysis of spermatogenesis after short-term testicular torsion in rats. Pediatr. Res. 94, 1650\u20131658 (2023).","journal-title":"Pediatr. Res."},{"key":"29283_CR56","doi-asserted-by":"crossref","unstructured":"Reyes, J. G. et al. The Hypoxic Testicle: Physiology and Pathophysiology. Oxid. Med. Cell. Longev. 2012, 929285 (2012).","DOI":"10.1155\/2012\/929285"},{"key":"29283_CR57","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1095\/biolreprod.102.013318","volume":"69","author":"JJ Lysiak","year":"2003","unstructured":"Lysiak, J. J., Nguyen, Q. A. T., Kirby, J. L. & Turner, T. T. Ischemia-reperfusion of the murine testis stimulates the expression of Proinflammatory cytokines and activation of c-jun N-terminal kinase in a pathway to E-selectin expression. Biol. Reprod. 69, 202\u2013210 (2003).","journal-title":"Biol. Reprod."},{"key":"29283_CR58","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1530\/REP-14-0240","volume":"149","author":"T Morielli","year":"2015","unstructured":"Morielli, T., O\u2019Flaherty, C., OXIDATIVE STRESS IMPAIRS FUNCTION & AND INCREASES REDOX PROTEIN MODIFICATIONS IN HUMAN SPERMATOZOA. Reprod. Camb. Engl. 149, 113\u2013123 (2015).","journal-title":"Reprod. Camb. Engl."},{"key":"29283_CR59","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s00345-008-0323-7","volume":"27","author":"M Bozlu","year":"2009","unstructured":"Bozlu, M., Acar, D., Cayan, S., Aktas, S. & Tunckiran, A. Protective effect of trapidil on long-term histologic damage in a rat model of testicular ischemia-reperfusion injury. World J. Urol. 27, 117\u2013122 (2009).","journal-title":"World J. Urol."},{"key":"29283_CR60","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.expneurol.2009.07.026","volume":"220","author":"S Carloni","year":"2009","unstructured":"Carloni, S., Girelli, S., Buonocore, G., Longini, M. & Balduini, W. Simvastatin acutely reduces ischemic brain damage in the immature rat via Akt and CREB activation. Exp. Neurol. 220, 82\u201389 (2009).","journal-title":"Exp. Neurol."},{"key":"29283_CR61","doi-asserted-by":"crossref","unstructured":"Wang, Z. et al. Rg1 alleviates oxidative stress and spermatogonium apoptosis in D-gal-induced testicular toxicity by activating Akt. Redox Rep. Commun. Free Radic Res 28, 2206197 (2023).","DOI":"10.1080\/13510002.2023.2206197"},{"key":"29283_CR62","doi-asserted-by":"publisher","first-page":"5800","DOI":"10.1128\/MCB.19.8.5800","volume":"19","author":"SG Kennedy","year":"1999","unstructured":"Kennedy, S. G., Kandel, E. S., Cross, T. K. & Hay, N. Akt\/Protein kinase B inhibits cell death by preventing the release of cytochrome c from mitochondria. Mol. Cell. Biol. 19, 5800\u20135810 (1999).","journal-title":"Mol. Cell. Biol."},{"key":"29283_CR63","doi-asserted-by":"publisher","first-page":"12041","DOI":"10.1074\/jbc.M010551200","volume":"276","author":"DR Plas","year":"2001","unstructured":"Plas, D. R., Talapatra, S., Edinger, A. L., Rathmell, J. C. & Thompson, C. B. Akt and Bcl-xL promote growth factor-independent survival through distinct effects on mitochondrial physiology. J. Biol. Chem. 276, 12041\u201312048 (2001).","journal-title":"J. Biol. Chem."},{"key":"29283_CR64","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S1097-2765(00)80307-X","volume":"3","author":"MG Vander Heiden","year":"1999","unstructured":"Vander Heiden, M. G., Chandel, N. S., Schumacker, P. T. & Thompson, C. B. Bcl-xL prevents cell death following growth factor withdrawal by facilitating mitochondrial ATP\/ADP exchange. Mol. Cell. 3, 159\u2013167 (1999).","journal-title":"Mol. Cell."},{"key":"29283_CR65","doi-asserted-by":"crossref","unstructured":"Vander Heiden, M. G. et al. Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival. Proc. Natl. Acad. Sci. U. S. A. 97, 4666\u20134671 (2000).","DOI":"10.1073\/pnas.090082297"},{"key":"29283_CR66","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/S1470-2045(05)70168-6","volume":"6","author":"JY Fang","year":"2005","unstructured":"Fang, J. Y. & Richardson, B. C. The MAPK signalling pathways and colorectal cancer. Lancet Oncol. 6, 322\u2013327 (2005).","journal-title":"Lancet Oncol."},{"key":"29283_CR67","first-page":"1113","volume":"18","author":"Q Li","year":"2014","unstructured":"Li, Q., Zhuang, Q. K., Yang, J. N. & Zhang, Y. Y. Statins excert neuroprotection on cerebral ischemia independent of their lipid-lowering action: the potential molecular mechanisms. Eur. Rev. Med. Pharmacol. Sci. 18, 1113\u20131126 (2014).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"29283_CR68","doi-asserted-by":"publisher","first-page":"993","DOI":"10.3892\/ol.2020.11684","volume":"20","author":"Y Lu","year":"2020","unstructured":"Lu, Y., Liu, B., Liu, Y., Yu, X. & Cheng, G. Dual effects of active ERK in cancer: A potential target for enhancing radiosensitivity. Oncol. Lett. 20, 993\u20131000 (2020).","journal-title":"Oncol. Lett."},{"key":"29283_CR69","doi-asserted-by":"publisher","first-page":"580","DOI":"10.4161\/cc.27379","volume":"13","author":"MP Lisanti","year":"2014","unstructured":"Lisanti, M. P. et al. JNK1 stress signaling is hyper-activated in high breast density and the tumor stroma. Cell. Cycle. 13, 580\u2013599 (2014).","journal-title":"Cell. Cycle"},{"key":"29283_CR70","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1095\/biolreprod.105.040741","volume":"73","author":"L Minutoli","year":"2005","unstructured":"Minutoli, L. et al. Evidence for a role of mitogen-activated protein kinase 3\/mitogen-activated protein kinase in the development of testicular ischemia-reperfusion injury. Biol. Reprod. 73, 730\u2013736 (2005).","journal-title":"Biol. Reprod."},{"key":"29283_CR71","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1046\/j.1365-2443.1998.00211.x","volume":"3","author":"WM Toone","year":"1998","unstructured":"Toone, W. M. & Jones, N. Stress-activated signalling pathways in yeast. Genes Cells Devoted Mol. Cell. Mech. 3, 485\u2013498 (1998).","journal-title":"Genes Cells Devoted Mol. Cell. Mech."},{"key":"29283_CR72","doi-asserted-by":"publisher","first-page":"2336","DOI":"10.1038\/sj.onc.1204384","volume":"20","author":"WM Toone","year":"2001","unstructured":"Toone, W. M., Morgan, B. A. & Jones, N. Redox control of AP-1-like factors in yeast and beyond. Oncogene 20, 2336\u20132346 (2001).","journal-title":"Oncogene"},{"key":"29283_CR73","doi-asserted-by":"publisher","first-page":"3492","DOI":"10.1007\/s12035-016-9926-y","volume":"54","author":"L Zheng","year":"2017","unstructured":"Zheng, L. et al. JNK activation contributes to oxidative Stress-Induced parthanatos in glioma cells via increase of intracellular ROS production. Mol. Neurobiol. 54, 3492\u20133505 (2017).","journal-title":"Mol. Neurobiol."},{"key":"29283_CR74","doi-asserted-by":"publisher","first-page":"32602","DOI":"10.1074\/jbc.M500684200","volume":"280","author":"RA Kaiser","year":"2005","unstructured":"Kaiser, R. A. et al. Genetic Inhibition or activation of JNK1\/2 protects the myocardium from ischemia-reperfusion-induced cell death in vivo. J. Biol. Chem. 280, 32602\u201332608 (2005).","journal-title":"J. Biol. Chem."},{"key":"29283_CR75","doi-asserted-by":"crossref","unstructured":"Shvedova, M., Anfinogenova, Y., Atochina-Vasserman, E. N., Schepetkin, I. A. & Atochin, D. N. c-Jun N-Terminal kinases (JNKs) in myocardial and cerebral Ischemia\/Reperfusion injury. Front Pharmacol 9, 715 (2018).","DOI":"10.3389\/fphar.2018.00715"},{"key":"29283_CR76","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1016\/j.atherosclerosis.2007.11.016","volume":"199","author":"N Schupp","year":"2008","unstructured":"Schupp, N., Schmid, U., Heidland, A. & Stopper, H. Rosuvastatin protects against oxidative stress and DNA damage in vitro via upregulation of glutathione synthesis. Atherosclerosis 199, 278\u2013287 (2008).","journal-title":"Atherosclerosis"},{"key":"29283_CR77","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/s41420-021-00718-3","volume":"7","author":"KE Shapira","year":"2021","unstructured":"Shapira, K. E. et al. Autophagy is induced and modulated by cholesterol depletion through transcription of autophagy-related genes and Attenuation of flux. Cell. Death Discov. 7, 320 (2021).","journal-title":"Cell. Death Discov"},{"key":"29283_CR78","doi-asserted-by":"publisher","first-page":"e518","DOI":"10.1038\/cddis.2013.44","volume":"4","author":"XF Qi","year":"2013","unstructured":"Qi, X. F. et al. HMG-CoA reductase inhibitors induce apoptosis of lymphoma cells by promoting ROS generation and regulating Akt, Erk and p38 signals via suppression of mevalonate pathway. Cell. Death Dis. 4, e518 (2013).","journal-title":"Cell. Death Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29283-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29283-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29283-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:02:35Z","timestamp":1777395755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-29283-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,22]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["29283"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-29283-w","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6611379\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,22]]},"assertion":[{"value":"7 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"45023"}}