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Cyclophosphamide (CP), a chemotherapeutic agent commonly used in the treatment of both malignant and non\u2010malignant conditions, is known to induce cytotoxicity in various tissues, particularly within the male reproductive system. This study aimed to investigate the protective effects of safranal against CP\u2010induced reproductive toxicity in Wistar albino rats. CP was administered orally at a dose of 15\u2009mg\/kg once per week for 56\u2009days to establish a model of testicular toxicity. In parallel, the treatment group received safranal via oral gavage at a daily dose of 200\u2009mg\/kg for the same duration. At the end of the treatment period, spermatological, biochemical, and histological analyses were performed on collected tissue samples. CP administration led to increased dead\/live and abnormal sperm ratios, elevated levels of NF\u2010\u03baB, IL\u20106, TNF\u2010\u03b1, and MDA, and a reduction in sperm motility and density, Nrf\u20102 expression, as well as GSH and GSH\u2010Px activity. In contrast, safranal treatment significantly ameliorated these detrimental effects. In conclusion, safranal demonstrated protective and therapeutic effects against CP\u2010induced reproductive toxicity, suggesting its potential as a supportive agent during chemotherapy.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.70452","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:35:51Z","timestamp":1750120551000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Safranal Alleviates Cyclophosphamide Induced Testicular Toxicity in Rats"],"prefix":"10.1002","volume":"13","author":[{"given":"Mustafa","family":"Cellat","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine Hatay Mustafa Kemal University  Hatay Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0130lker","family":"Yava\u015f","sequence":"additional","affiliation":[{"name":"Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine Hatay Mustafa Kemal University  Hatay Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Uyar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine Hatay Mustafa Kemal University  Hatay Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammed","family":"Etyemez","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine Kastamonu University  Kastamonu Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9716-0697","authenticated-orcid":false,"given":"Mehmet","family":"G\u00fcven\u00e7","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Veterinary Medicine Hatay Mustafa Kemal University  Hatay Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"Methods of Enzymatic Analysis","author":"Aebi H.","year":"1983"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2018.08.007"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.repbio.2024.100990"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712799320538"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2018.08.006"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13899"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.1749"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/sms.12702"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2020.1856130"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2020.126574"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2010.00571.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijir.2009.9"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9050429"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1529871"},{"key":"e_1_2_10_16_1","first-page":"291","article-title":"Adducts to Nuclear DNA and Mitochondrial DNA as Biomarkers in Chemoprevention","volume":"139","author":"De Flora S.","year":"1996","journal-title":"IARC Scientific Publications"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200544110-00003"},{"key":"e_1_2_10_18_1","article-title":"Cyclophosphamide\u2010Induced Testicular Oxidative\u2010Inflammatory Injury Is Accompanied by Altered Immunosuppressive Indoleamine 2, 3\u2010Dioxygenase in Wister Rats: Influence of Dietary Quercetin","volume":"54","author":"Ebokaiwe A. 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