{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:00:07Z","timestamp":1775275207846,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"French Agence Nationale de la Recherche","award":["2020 07132"],"award-info":[{"award-number":["2020 07132"]}]},{"name":"French Agence Nationale de la Recherche","award":["2020 07132"],"award-info":[{"award-number":["2020 07132"]}]},{"name":"R\u00e9gion Pays de la Loire","award":["2020 07132"],"award-info":[{"award-number":["2020 07132"]}]},{"name":"R\u00e9gion Pays de la Loire","award":["2020 07132"],"award-info":[{"award-number":["2020 07132"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The present experiment aimed to identify the potential protective role of empagliflozin (EMPA) on haloperidol (HAL)-induced ovarian damage in female rats because of its anti-inflammatory, antioxidant, and antiapoptotic effects. EMPA was administered in the presence and absence of HAL. Thirty-two adult female albino rats were divided into four groups. Control group, EMPA group: received EMPA (10 mg\/kg\/day) p.o., HAL group: received HAL (2 mg\/kg\/day) p.o., HAL + EMPA group: HAL (2 mg\/kg\/day) combined with EMPA for 28 days. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-mullerian hormone (AMH) levels were measured. Ovarian oxidative stress parameters, besides inflammatory and apoptotic biomarkers, and ovarian Sirtuin-1 (Sirt-1) were evaluated. Ovarian histopathological examination and heat shock protein 70 (Hsp70) immunohistochemical study were performed. HAL significantly increased serum levels of FSH, LH, and ovarian inflammatory, apoptotic, and oxidative stress biomarkers and decreased serum AMH levels and Sirt-1 expression. Histopathological findings of ovarian damage and high Hsp70 immunoexpression were detected. EMPA significantly normalized the distributed hormonal levels, oxidative stress, inflammatory, and apoptotic biomarkers with a prompt improvement in the histopathological picture and a decrease in Hsp70 immunoexpression. Accordingly, EMPA protected against HAL-induced ovarian toxicity by modulating the Sirt-1\/Hsp70\/TNF-\u03b1\/caspase-3 signaling pathway.<\/jats:p>","DOI":"10.3390\/ph16020168","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T01:29:45Z","timestamp":1674523785000},"page":"168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Empagliflozin Protects against Haloperidol Experimentally-Induced Ovarian Toxicity"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6511-1797","authenticated-orcid":false,"given":"Walaa Yehia","family":"Abdelzaher","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-9615","authenticated-orcid":false,"given":"Michel","family":"De Waard","sequence":"additional","affiliation":[{"name":"L\u2019institut Du Thorax, INSERM, CNRS, UNIV NANTES, F-44007 Nantes, France"},{"name":"Smartox Biotechnology, 6 Rue des Platanes, F-38120 Saint-Egr\u00e8ve, France"},{"name":"LabEx \u00abIon Channels, Science & Therapeutics\u00bb, Universit\u00e9 de Nice Sophia-Antipolis, F-06560 Valbonne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyaa Abdelfattah","family":"Abdelmonaem","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalia Mohamed","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2660-9909","authenticated-orcid":false,"given":"Nashwa Fathy Gamal","family":"El-Tahawy","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rehab Ahmed","family":"Rifaai","sequence":"additional","affiliation":[{"name":"Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hatem A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5230-1372","authenticated-orcid":false,"given":"Kareem","family":"Shaheen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Ahmed","family":"Zeen El-Din","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7854-2086","authenticated-orcid":false,"given":"Nermeen N.","family":"Welson","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni Suef 62511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shereen ELsayed","family":"Tawfeek","sequence":"additional","affiliation":[{"name":"Anatomy Department, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"},{"name":"Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Sharkia 44519, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7817-425X","authenticated-orcid":false,"given":"Gaber El-Saber","family":"Batiha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6184-2901","authenticated-orcid":false,"given":"Asmaa Mohamed","family":"Abdel-Aziz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Minia University, Minia 61511, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/0706743718773728","article-title":"An Overview of Animal Models Related to Schizophrenia","volume":"64","author":"Winship","year":"2019","journal-title":"Can. 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