{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:58:36Z","timestamp":1791907116845,"version":"4.3.4"},"reference-count":71,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Ovarian ischemia is a pathological condition that usually occurs due to ovarian torsion, resulting in the interruption of blood supply to the ovaries and oxygen deficiency. Silymarin (SLM) is a flavonoid complex of plant origin with pharmacological properties such as antioxidant, anti\u2010inflammatory, and antiapoptotic effects. In this study, we investigated the effects of SLM through different pathways in rats subjected to experimental ovarian ischemia\/reperfusion (I\/R). Female Wistar rats were divided into five groups: Control, SLM (50\u2009mg\/kg), I\/R, I\/R\u2009+\u2009SLM25 (25\u2009mg\/kg), and I\/R\u2009+\u2009SLM50 (50\u2009mg\/kg). SLM was given orally for 7 days, followed by ischemia (2\u2009h) and reperfusion (2\u2009h) on day 8. Biochemical (MDA, GSH, SOD, CAT, GPx) and histological (H&amp;E, Ki\u201067 IHC) analyses were performed. Also, molecular (qRT\u2010PCR) analyses were performed to evaluate oxidative stress, inflammation, apoptosis, and Wnt signaling. I\/R increased MDA and NO levels in ovarian tissue while decreasing SOD, CAT, GPx, and GSH. Antioxidant defense genes (Nrf\u20102, HO\u20101, NQO1) were suppressed, and inflammation markers (NF\u2010\u0138B, IL\u20101\u03b2, TNF\u2010\u03b1) along with apoptotic markers (Bax, Caspase\u20103) were elevated, while Bcl\u20102 decreased. The Wnt signaling pathway was inhibited, particularly at Wnt\u20103A, LRP5, Dvl\u20102, and Cyclin\u20101, reducing Ki\u201067 protein levels and IHC positivity. Silymarin has shown a therapeutic effect on ovarian ischemia reperfusion injury with its antioxidant, antiapoptotic and anti\u2010inflammatory effects and cell cycle regulatory activity.<\/jats:p>","DOI":"10.1002\/jbt.70138","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T10:54:16Z","timestamp":1736938456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Investigation of the Effects of Silymarin on Ovarian Ischemia Reperfusion via Nrf\u20102\/HO\u20101\/NQO1, Ki\u201067 and Wnt Signaling Pathways"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7773-5978","authenticated-orcid":false,"given":"Ay\u015fe Bet\u00fcl","family":"\u00d6zt\u00fcrk","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, Faculty of Medicine Aksaray University Aksaray Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8457-9448","authenticated-orcid":false,"given":"Nurhan","family":"Akaras","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine Aksaray University Aksaray Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan","family":"\u015eim\u015fek","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Aksaray University Aksaray Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih Mehmet","family":"Kandemir","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Medicine Aksaray University Aksaray Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/01443615.2021.1916813"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000995"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2022.2043901"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-01854-w"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/tcmj.tcmj_55_17"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.12398"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-019-03177-w"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-022-03803-x"},{"issue":"21","key":"e_1_2_11_10_1","first-page":"10446","article-title":"Protective Effects of Silymarin on Testicular Torsion\/Detorsion in Rats","volume":"27","author":"Azizo\u011flu M.","year":"2023","journal-title":"European Review for Medical & Pharmacological Sciences"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2020.145239"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23528"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(66)90167-9"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(68)90092-4"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/3415046"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116840"},{"issue":"12","key":"e_1_2_11_18_1","article-title":"Effects of Ukrain on Intestinal Apoptosis Caused by Ischemia\u2010Reperfusion Injury in Rats","volume":"8","author":"Akc\u0131lar R.","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"issue":"2","key":"e_1_2_11_19_1","first-page":"209","article-title":"Assessment of Expressions of Bcl\u2010XL, b\u2010FGF, Bmp\u20102, Caspase\u20103, PDGFR\u2010\u03b1, Smad1 and TGF\u2010\u03b21 Genes in a Rat Model of Lung Ischemia\/Reperfusion","volume":"19","author":"\u015eim\u015fek H.","year":"2016","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2016.09.067"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2016-0309"},{"issue":"9","key":"e_1_2_11_22_1","first-page":"1098","article-title":"Protective Effects of Zingerone Against Sodium Arsenite\u2010Induced Lung Toxicity: A Multi\u2010Biomarker Approach","volume":"26","author":"\u015eim\u015fek H.","year":"2023","journal-title":"Iranian Journal of Basic Medical Sciences"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.23604"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-023-28747-8"},{"issue":"2","key":"e_1_2_11_25_1","first-page":"167","article-title":"Beneficial Effects of Silymarin and Naringin Against Methotrexate\u2010Induced Hepatotoxicity in Rats","volume":"12","author":"Kandemir F. 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