{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:54:03Z","timestamp":1785405243453,"version":"3.56.0"},"reference-count":46,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006701","name":"Umm Al-Qura University","doi-asserted-by":"crossref","award":["26UQU4310007GSSR02"],"award-info":[{"award-number":["26UQU4310007GSSR02"]}],"id":[{"id":"10.13039\/501100006701","id-type":"DOI","asserted-by":"crossref"}]},{"award":["26UQU4310007GSSR02"],"award-info":[{"award-number":["26UQU4310007GSSR02"]}],"id":[{"id":"https:\/\/ror.org\/01xjqrm90","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ferroptosis, a type of iron overload-induced cell death, is involved in diabetes-induced testicular dysfunction. Hence, this study was designed to investigate, for the first time, the impact of lipoxin A4 (LXA4) administration on testicular tissue in diabetic rats and explore its probable role in regulating ferroptosis in comparison with the standard ferroptosis inhibitor (ferrostatin-1, Fer-1). Albino rats of Wistar strain were divided into a control group, a type II diabetes mellitus (DM) group, a DM + Fer-1group, and a DM + LXA4 group. Serum levels of iron, insulin, glucose, total cholesterol, triglycerides, and testosterone were assayed. Testicular tissue markers of oxidative stress, ferroptosis, and inflammation were also assessed by different methods. Our results confirmed diabetes-induced testicular injury and disruption of its function via inducement of ferroptosis, but this was ameliorated with LXA4 and Fer-1 administration. However, Fer-1 showed a greater protective effect compared to LXA4 under the conditions of this study. We concluded that LXA4 partially secured the testicular tissue of diabetic rats against ferroptosis via augmenting the antioxidant Nrf2\/SLC7A11\/GPX4 pathway. Therefore, LXA4 may have a possible protective effect on the testicular tissue of diabetic patients.<\/jats:p>","DOI":"10.3390\/ijms27083548","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:04:42Z","timestamp":1776330282000},"page":"3548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Eicosanoid Derivative, Lipoxin A4, Guards Against Testicular Ferroptosis in Rat Model of Type II Diabetes by Regulating Nrf2\/SLC7A11\/GPX4 Pathway"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6303-9752","authenticated-orcid":false,"given":"Elshymaa A.","family":"Abdel-Hakeem","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Minia University, Minia 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manar","family":"Fouli Gaber Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia 61111, Egypt"},{"name":"Faculty of Physical Therapy, Lotus University, Minia 61768, Egypt"},{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Minia National University, Minia 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doaa","family":"Mohamed Elroby Ali","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"},{"name":"Department of Biochemistry, Faculty of Pharmacy, Badr University Branch Assiut, Assiut 71511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimaa","family":"Abdel Baset Abdel Hakim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine, Minia University, Minia 61111, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-0499","authenticated-orcid":false,"given":"Ahmed M.","family":"Ashour","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8241-4184","authenticated-orcid":false,"given":"Ali","family":"Khames","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Sohag University, Sohag 82524, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2465-6381","authenticated-orcid":false,"given":"Heba A.","family":"Abdel-Hamid","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine, Minia University, Minia 61111, Egypt"},{"name":"Department of Medical Physiology, Faculty of Medicine, Al-Baha University, Al-Baha 65779, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"102201","DOI":"10.1016\/j.arr.2024.102201","article-title":"Ferroptosis: Mechanisms and role in diabetes mellitus and its complications","volume":"94","author":"Liu","year":"2024","journal-title":"Ageing Res. 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