{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:07:32Z","timestamp":1793156852388,"version":"4.5.0"},"reference-count":54,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Tramadol, a weak opioid analgesic agent, is known to induce ovarian damage. Previous studies have held oxidative stress responsible for the adverse effects of tramadol on female reproduction. This study examined the protective effects of ATP against tramadol-induced ovarian damage and reproductive dysfunction in rats. Methods: Rats were divided into four groups (n = 12); healthy (HG), only ATP (ATPG), only tramadol (TMDG), and ATP + tramadol (ATMG). ATP was injected intraperitoneally at 25 mg\/kg. Tramadol at 50 mg\/kg was initiated one hour after ATP. The treatment was administered once a day for 14 days. Six rats from each group were euthanized. For two months, the remaining rats were paired with male rats. Rats that failed to give birth during this period were considered infertile. A maternity period was calculated for the rats that were delivered. Results: Tramadol caused an increase in malondialdehyde and interleukin-6, and decreased total glutathione, superoxide dismutase, and catalase levels in the ovarian tissue. Furthermore, tramadol disrupted the histological structure of the ovaries, and immunohistochemical staining revealed severe immunopositivity. Tramadol again caused infertility and delayed pregnancy in fertile women. By suppressing biochemical changes, ATP significantly reduced tramadol-induced ovarian damage. Both histopathologically and immunohistochemically, ATP treatment regressed ovarian damage. Additionally, ATP significantly reduced tramadol-induced infertility and maternal delay. Conclusions: The results indicate that tramadol-induced oxidative and inflammatory ovarian injury, infertility, and caspase 3 were suppressed by ATP, as demonstrated by our experimental findings.<\/jats:p>","DOI":"10.3390\/ph18020216","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T04:47:31Z","timestamp":1738817251000},"page":"216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of Tramadol-Induced Ovarian Damage and Reproductive Dysfunction with Adenosine Triphosphate and the Protective Role of Exogenous ATP Treatment"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4746-5414","authenticated-orcid":false,"given":"Neset","family":"Gumusburun","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics, Medical Park Tokat Hospital, Tokat 60030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilhan Bahri","family":"Delibasi","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Medical Park Tokat Hospital, Tokat 60030, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seval","family":"Bulut","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9239-4099","authenticated-orcid":false,"given":"Halis","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Kalkan Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha Abdulkadir","family":"Coban","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan 24100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Sefa","family":"Mendil","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine, Erciyes University, Kayseri 38039, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0128-7990","authenticated-orcid":false,"given":"Zeynep","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Nursing, Faculty of Health Sciences, Erzincan Binali Yildirim University, Erzincan 24100, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101893","DOI":"10.1016\/j.jchemneu.2020.101893","article-title":"Evaluation of vitamin C protective effect on the cerebrocortical antioxidant defense, histopathological, pro-apoptotic p53 and anti-apoptotic Bcl2 expressions against tramadol neurotoxicity in rats","volume":"112","author":"Kader","year":"2021","journal-title":"J. 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