{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:55Z","timestamp":1787027635451,"version":"build-2736575974"},"reference-count":87,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2025R713"],"award-info":[{"award-number":["PNURSP2025R713"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cisplatin (CDDP) is a widely used chemotherapeutic agent, but its off-target toxicity, including testicular damage, limits clinical use. Bioactive compounds may help mitigate chemotherapy-induced reproductive toxicity. This study investigates thymol\u2019s role in modulating ferritinophagy to preserve reproductive function and steroidogenesis. Male Wistar rats were randomized to control, CDDP, thymol, or CDDP + thymol groups. Thymol (60 mg\/kg) was given orally for 14 days, and CDDP (8 mg\/kg) was administered intraperitoneally on day 7. Testicular function was assessed through hormonal analysis, sperm evaluation, and histopathology. Ferritinophagy, oxidative stress, and inflammatory markers were assessed to elucidate thymol\u2019s chemoprotective mechanisms. Thymol co-administration preserved steroidogenesis, restored sperm quality, and maintained testicular architecture in CDDP-treated rats. Thymol suppressed ferritinophagy, reducing iron overload and mitigating reactive oxygen species (ROS)-induced cellular damage. Additionally, thymol activated the Keap1\/Nrf2\/HO-1 pathway, enhancing antioxidant defenses while downregulating inflammatory mediators (TNF-\u03b1, IL-6). Additionally, thymol enhanced CDDP\u2019s selectivity toward cancer cells while reducing its toxicity to normal cells. This study provides evidence that thymol modulates ferritinophagy to attenuate CDDP-induced testicular toxicity, helping preserve reproductive function via regulation of iron homeostasis. These findings highlight thymol\u2019s potential as an adjunct therapy to mitigate chemotherapy-associated reproductive damage while maintaining CDDP\u2019s anticancer efficacy.<\/jats:p>","DOI":"10.3390\/biom15091277","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T15:15:57Z","timestamp":1756912557000},"page":"1277","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Thymol Preserves Spermatogenesis and Androgen Production in Cisplatin-Induced Testicular Toxicity by Modulating Ferritinophagy, Oxidative Stress, and the Keap1\/Nrf2\/HO-1 Pathway"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3983-868X","authenticated-orcid":false,"given":"Amira M.","family":"Badr","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"},{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5934-6917","authenticated-orcid":false,"given":"Sheka","family":"Aloyouni","sequence":"additional","affiliation":[{"name":"Genetics Section, Research Department, Natural and Health Sciences Research Center, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmin","family":"Mahran","sequence":"additional","affiliation":[{"name":"Research Department, Natural and Health Sciences Research Center, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2434-8963","authenticated-orcid":false,"given":"Hanan","family":"Henidi","sequence":"additional","affiliation":[{"name":"Research Department, Natural and Health Sciences Research Center, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1160-5040","authenticated-orcid":false,"given":"Elshaymaa I.","family":"Elmongy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haya M.","family":"Alsharif","sequence":"additional","affiliation":[{"name":"College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0181-6330","authenticated-orcid":false,"given":"Aliyah","family":"Almomen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0648-0979","authenticated-orcid":false,"given":"Sahar","family":"Soliman","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Osteopathic Medicine, Sam Houston State University, Conroe, TX 77304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"ref_1","first-page":"833","article-title":"Cisplatin-associated neuropathy characteristics compared with those associated with other neurotoxic chemotherapy agents (Alliance A151724)","volume":"29","author":"Albany","year":"2021","journal-title":"Support. 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