{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T04:56:35Z","timestamp":1775451395269,"version":"3.50.1"},"reference-count":42,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Projects Unit of Recep Tayyip Erdo\u011fan University","award":["TSA-2025-2023"],"award-info":[{"award-number":["TSA-2025-2023"]}]},{"name":"Recep Tayyip Erdo\u011fan University Development Foundation","award":["02026002025143"],"award-info":[{"award-number":["02026002025143"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>To evaluate seminal oxidative stress, antioxidant defense, apoptosis-related activity, and Sertoli cell biomarkers in infertile men with grade 3 varicocele versus normozoospermic controls, and to assess postoperative changes after varicocelectomy. This prospective observational case\u2013control study included 39 infertile men with grade 3 clinical varicocele and 44 normozoospermic controls. Seminal plasma levels of Malondialdehyde (MDA), 8-hydroxy-2\u2032-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), glutathione peroxidase-1 (GPx-1), reduced glutathione (GSH), nuclear factor erythroid 2\u2013related factor 2 (NRF2), Kelch-like ECH-associated protein 1 (KEAP1), caspase-3, anti-M\u00fcllerian hormone (AMH), and inhibin B were measured by ELISA. Testicular volume, semen parameters, and diagnostic performance were also evaluated. Compared with controls, patients with varicocele had lower testicular volumes and impaired semen parameters. Seminal 8-OHdG and caspase-3 levels were higher, whereas SOD and inhibin B levels were lower. Baseline MDA, GPx-1, GSH, NRF2, KEAP1, and AMH levels did not differ significantly. After varicocelectomy, sperm concentration, total sperm count, progressive and total motility, total motile sperm count, morphology, and round cell count improved significantly. Postoperatively, caspase-3, MDA, and KEAP1 decreased, whereas SOD, GPx-1, GSH, NRF2, and inhibin B increased significantly. 8-OHdG showed a borderline decrease, and AMH remained unchanged. SOD showed the best diagnostic performance. Grade 3 varicocele is associated with oxidative DNA damage, impaired antioxidant defense, increased apoptotic signaling, and altered Sertoli cell-related seminal biomarkers. Varicocelectomy partially restores redox homeostasis, which may contribute to improved spermatogenic function.<\/jats:p>","DOI":"10.3390\/antiox15040455","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:11:28Z","timestamp":1775445088000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative Damage, Antioxidant Capacity, and Apoptotic Activation in Varicocele: Biochemical Evidence of Improvement After Surgical Repair"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1422-7137","authenticated-orcid":false,"given":"Erdem","family":"Orman","sequence":"first","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5189-3166","authenticated-orcid":false,"given":"Hakki","family":"Uzun","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8988-4321","authenticated-orcid":false,"given":"Merve","family":"Huner Yigit","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9780-2808","authenticated-orcid":false,"given":"Ertugrul","family":"Yigit","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, Trabzon 61080, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8032-6040","authenticated-orcid":false,"given":"Huseyin Cinar","family":"Zihni","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Graduate School of Health Sciences, Karadeniz Technical University, Trabzon 61080, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7019-4264","authenticated-orcid":false,"given":"Gorkem","family":"Akca","sequence":"additional","affiliation":[{"name":"Department of Urology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize 53100, T\u00fcrkiye"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s12958-015-0032-1","article-title":"A unique view on male infertility around the globe","volume":"13","author":"Agarwal","year":"2015","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S0140-6736(20)32667-2","article-title":"Male infertility","volume":"397","author":"Agarwal","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nrurol.2017.98","article-title":"Varicocele and male infertility","volume":"14","author":"Jensen","year":"2017","journal-title":"Nat. Rev. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.ucl.2013.08.001","article-title":"The varicocele","volume":"41","author":"Masson","year":"2014","journal-title":"Urol. Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Bouhadana, D., Godin Pag\u00e9, M.H., Montjean, D., B\u00e9langer, M.-C., Benkhalifa, M., Miron, P., and Petrella, F. (2025). The role of antioxidants in male fertility: A comprehensive review of mechanisms and clinical applications. Antioxidants, 14.","DOI":"10.3390\/antiox14081013"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Wood, G.J.A., Cardoso, J.P.G., Paluello, D.V., Nunes, T.F., and Cocuzza, M. (2021). Varicocele-associated infertility and the role of oxidative stress on sperm DNA fragmentation. Front. Reprod. Health, 3.","DOI":"10.3389\/frph.2021.695992"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-3-030-89340-8_10","article-title":"Oxidative stress and varicocele-associated male infertility","volume":"1358","author":"Lai","year":"2022","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, K., Gao, Y., Wang, C., Liang, M., Liao, Y., and Hu, K. (2022). Role of oxidative stress in varicocele. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.850114"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/aja.2010.68","article-title":"Apoptosis and DNA damage in human spermatozoa","volume":"13","author":"Aitken","year":"2011","journal-title":"Asian J. Androl."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1016\/S1472-6483(10)61190-X","article-title":"Relationship between oxidative stress, varicocele and infertility: A meta-analysis","volume":"12","author":"Agarwal","year":"2006","journal-title":"Reprod. Biomed. Online"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ribas-Maynou, J., and Yeste, M. (2020). Oxidative stress in male infertility: Causes, effects in assisted reproductive techniques, and protective support of antioxidants. Biology, 9.","DOI":"10.3390\/biology9040077"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.aju.2017.11.001","article-title":"Role of reactive oxygen species in male infertility: An updated review of literature","volume":"16","author":"Wagner","year":"2018","journal-title":"Arab. J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e230024","DOI":"10.1530\/RAF-23-0024","article-title":"Role of oxidative stress in male infertility","volume":"4","author":"Takalani","year":"2023","journal-title":"Reprod. Fertil."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1089\/ars.2012.4905","article-title":"Regulation of the intrinsic apoptosis pathway by reactive oxygen species","volume":"19","author":"Wu","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00018-019-03253-8","article-title":"Oxidative stress and male infertility: Current knowledge of pathophysiology and role of antioxidant therapy in disease management","volume":"77","author":"Barati","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e13581","DOI":"10.1111\/and.13581","article-title":"Oxidative stress in the pathophysiology of male infertility","volume":"53","author":"Ritchie","year":"2021","journal-title":"Andrologia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1111\/andr.12511","article-title":"A global view of the pathophysiology of varicocele","volume":"6","author":"Hassanin","year":"2018","journal-title":"Andrology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.bbamcr.2018.02.010","article-title":"Nrf2-Keap1 signaling in oxidative and reductive stress","volume":"1865","author":"Bellezza","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.fertnstert.2021.04.003","article-title":"Effect of varicocelectomy on sperm deoxyribonucleic acid fragmentation rates in infertile men with clinical varicocele: A systematic review and meta-analysis","volume":"116","author":"Roque","year":"2021","journal-title":"Fertil. Steril."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1007\/s11255-018-1839-4","article-title":"Effect of varicocele repair on sperm DNA fragmentation: A review","volume":"50","author":"Roque","year":"2018","journal-title":"Int. Urol. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15579883231199400","DOI":"10.1177\/15579883231199400","article-title":"Effects of varicocele surgical repair on serum hormone and inhibin B levels for patients with varicocele: A systematic review and meta-analysis","volume":"17","author":"Tian","year":"2023","journal-title":"Am. J. Men\u2019s Health"},{"key":"ref_22","unstructured":"World Health Organization (2021). WHO Laboratory Manual for the Examination and Processing of Human Semen, World Health Organization. [6th ed.]."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3217","DOI":"10.1007\/s11255-024-04080-y","article-title":"Don\u2019t wait any longer, conceive in time: A systematic review and meta-analysis based on semen parameters after varicocelectomy","volume":"56","author":"Mei","year":"2024","journal-title":"Int. Urol. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Practice Committee of the American Society for Reproductive Medicine, and Society for Male Reproduction and Urology (2014). Report on varicocele and infertility: A committee opinion. Fertil. Steril., 102, 1556\u20131560.","DOI":"10.1016\/j.fertnstert.2014.10.007"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"748","DOI":"10.5534\/wjmh.240290","article-title":"Recent guidelines and perspectives for varicocele: A clinical consensus and recommendations from the Korean Society for Sexual Medicine and Andrology","volume":"43","author":"Kim","year":"2025","journal-title":"World J. Men\u2019s Health"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/aja.2008.48","article-title":"The reliability of ultrasonographic measurements for testicular volume assessment: Comparison of three common formulas with true testicular volume","volume":"11","author":"Hsieh","year":"2009","journal-title":"Asian J. Androl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1111\/andr.13053","article-title":"Varicocoele. Classification and pitfalls","volume":"9","author":"Bertolotto","year":"2021","journal-title":"Andrology"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hassanzad, M., and Hajian-Tilaki, K. (2024). Methods of determining optimal cut-point of diagnostic biomarkers with application of clinical data in ROC analysis: An update review. BMC Med. Res. Methodol., 24.","DOI":"10.1186\/s12874-024-02198-2"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1530\/RAF-20-0048","article-title":"Evaluation of oxidative stress in seminal plasma of adolescents with varicocele","volume":"2","author":"Barradas","year":"2021","journal-title":"Reprod. Fertil."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/andr.12210","article-title":"A comprehensive investigation of sperm DNA damage and oxidative stress injury in infertile patients with subclinical, normozoospermic, and astheno\/oligozoospermic clinical varicocoele","volume":"4","author":"Ni","year":"2016","journal-title":"Andrology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/j.1464-410X.2011.10240.x","article-title":"Effect of varicocele on sperm function and semen oxidative stress","volume":"109","author":"Blumer","year":"2012","journal-title":"BJU Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1080\/14647273.2020.1870756","article-title":"Seminal inflammasome activity in the adult varicocele","volume":"25","author":"Camargo","year":"2022","journal-title":"Hum. Fertil."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ja\u0161inskien\u0117, E., and \u010caplinskien\u0117, M. (2025). The Link Between Oxidative Stress and Male Infertility in Lithuania: A Retrospective Study. Medicina, 61.","DOI":"10.3390\/medicina61091715"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e29752","DOI":"10.1016\/j.heliyon.2024.e29752","article-title":"Role of nuclear factor erythroid 2-related factor 2 (Nrf2) in female and male fertility","volume":"10","author":"Valipour","year":"2024","journal-title":"Heliyon"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Signorini, C., Saso, L., Ghareghomi, S., Telkoparan-Akillilar, P., Collodel, G., and Moretti, E. (2024). Redox homeostasis and Nrf2-regulated mechanisms are relevant to male infertility. Antioxidants, 13.","DOI":"10.3390\/antiox13020193"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"513","DOI":"10.4103\/aja.aja_114_19","article-title":"Seminal plasma miR-210-3p induces spermatogenic cell apoptosis by activating caspase-3 in patients with varicocele","volume":"22","author":"Xu","year":"2020","journal-title":"Asian J. Androl."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"87","DOI":"10.5534\/wjmh.210153","article-title":"Oxidative stress: A comprehensive review of biochemical, molecular, and genetic aspects in the pathogenesis and management of varicocele","volume":"40","author":"Finelli","year":"2022","journal-title":"World J. Men\u2019s Health"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"389","DOI":"10.2164\/jandrol.111.013433","article-title":"Effects of varicocelectomy on sperm DNA fragmentation, mitochondrial function, chromatin condensation, and apoptosis","volume":"33","author":"Condorelli","year":"2012","journal-title":"J. Androl."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.1016\/j.fertnstert.2009.11.046","article-title":"Seminal plasma levels of anti-M\u00fcllerian hormone and inhibin B are not predictive of testicular sperm retrieval in nonobstructive azoospermia: A study of 139 men","volume":"94","author":"Mitchell","year":"2010","journal-title":"Fertil. Steril."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2049","DOI":"10.1007\/s10815-021-02176-3","article-title":"Hormonal markers as noninvasive predictors of sperm retrieval in non-obstructive azoospermia","volume":"38","author":"Zarezadeh","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1046\/j.1365-2265.2001.01302.x","article-title":"Increased serum inhibin B levels after varicocele treatment","volume":"54","author":"Pierik","year":"2001","journal-title":"Clin. Endocrinol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/j.1365-2605.2007.00747.x","article-title":"Varicocele sclerotherapy improves serum inhibin B levels and seminal parameters","volume":"30","author":"Bertagna","year":"2007","journal-title":"Int. J. Androl."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T03:34:51Z","timestamp":1775446491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/15\/4\/455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,5]]},"references-count":42,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["antiox15040455"],"URL":"https:\/\/doi.org\/10.3390\/antiox15040455","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,5]]}}}