{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T03:49:33Z","timestamp":1769312973021,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,23]],"date-time":"2020-01-23T00:00:00Z","timestamp":1579737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The aim of this study was to investigate the possible prophylactic effects of agomelatine (AGO) against testicular and epididymal damage induced by methotrexate (MTX) in rats. Twenty\u2010four male Wistar albino rats were divided into three groups: Group I (control group), Group II (MTX group: 20\u2009mg\/kg MTX, i.p, single dose), and Group III (MTX+AGO group: 20\u2009mg\/kg MTX, i.p, single dose+40\u2009mg\/kg AGO; gavage, 7 days). The rats were killed under anesthesia 24\u2009hours after the last AGO application. Testicular and epididymal tissues were bilaterally removed for morphometric, biochemical, pathological, and immunohistochemical analyses. Body, testicular, and epididymal weights were measured. Malondialdehyde (MDA), superoxide dismutase, catalase, and glutathione peroxidase levels were measured in testes. Sperm count, hyperemia, edema, inflammatory reaction, degenerated and necrotic cells were evaluated by histopathological analysis. In addition, inducible nitric oxide synthase (iNOS), granulocyte colony\u2010stimulating factor (G\u2010CSF), osteopontin (OPN), and heat shock protein\u201070 (HSP70) immune reactions were analyzed in testes and epididymides. Decreased epididymal weights, increased MDA levels, decreased sperm count, hyperemia, edema, inflammatory reaction, and degenerated and necrotic cells were observed in the MTX group. In addition, iNOS, HSP70, G\u2010CSF, and OPN immune reactions were increased. AGO improved morphometric, biochemical, histopathological, and immunohistochemical findings. The present study confirms that MTX induces testicular and epididymal damage both biochemically and immunohistochemically. However, AGO demonstrated ameliorative effects on both biochemical and pathological findings of the current study.<\/jats:p>","DOI":"10.1002\/jbt.22445","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T05:37:10Z","timestamp":1579844230000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Ameliorating effects of agomelatine on testicular and epididymal damage induced by methotrexate in rats"],"prefix":"10.1002","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9516-0864","authenticated-orcid":false,"given":"Rahime","family":"Aslankoc","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Department of Physiology Suleyman Demirel University Isparta Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozlem","family":"Ozmen","sequence":"additional","affiliation":[{"name":"Faculty of Veterinary Medicine, Department of Pathology Mehmet Akif Ersoy University Burdur Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamit Yasar","family":"Ellidag","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Antalya Education and Research Hospital Antalya Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,1,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13057"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.02.002"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20255"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2004.03.001"},{"key":"e_1_2_9_6_1","first-page":"5511","volume":"7","author":"Daggulli M.","year":"2014","journal-title":"Int. J. Clin. Exp. Med."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.11.078"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2011.04.012"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpobgyn.2011.11.008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2008.11.011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.09.015"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327108092293"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.11.054"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/10520295.2017.1350748"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-6020-6_5"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/11534420-000000000-00000"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.895505"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(90)86135-I"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0034-5288(18)32219-7"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"e_1_2_9_22_1","first-page":"158","volume":"70","author":"Paglia D. E.","year":"1967","journal-title":"J. Lab. Clin. Med."},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2008.00897.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrgentox.2008.07.003"},{"key":"e_1_2_9_25_1","first-page":"1570","volume":"269","author":"Kaneko T.","year":"2002","journal-title":"FEBS. J."},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/489659"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.12971"},{"key":"e_1_2_9_28_1","first-page":"541","volume":"9","author":"Sheikhbahaei F.","year":"2016","journal-title":"\u0130nt. J. Fertil. Steril"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327110382564"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18050919"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod63.5.1285"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1530\/ror.0.0040023"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod66.5.1437"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026-010-8179-5"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.4142\/jvs.2007.8.2.107"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23559"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2008.310"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1179\/174313209X393582"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2009.01023.x"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbt.22445","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22445","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.22445","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22445","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T03:36:24Z","timestamp":1694057784000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.22445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,23]]},"references-count":38,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/jbt.22445"],"URL":"https:\/\/doi.org\/10.1002\/jbt.22445","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,23]]},"assertion":[{"value":"2019-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-08","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22445"}}