{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:47:16Z","timestamp":1791920836242,"version":"4.3.4"},"reference-count":62,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T00:00:00Z","timestamp":1667088000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Open Access Fund of Leibniz Universit\u00e4t Hannover"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Hepatic fibrosis causes severe morbidity and death. No viable treatment can repair fibrosis and protect the liver until now. We intended to discover the empagliflozin\u2019s (EMPA) hepatoprotective efficacy in thioacetamide (TAA)-induced hepatotoxicity by targeting AMPK\/SIRT-1 activity and reducing HIF-1\u03b1. Rats were treated orally with EMPA (3 or 6 mg\/kg) with TAA (100 mg\/kg, IP) thrice weekly for 6 weeks. EMPA in both doses retracted the serum GGT, ALT, AST, ammonia, triglycerides, total cholesterol, and increased serum albumin. At the same time, EMPA (3 or 6 mg\/kg) replenished the hepatic content of GSH, ATP, AMP, AMPK, or SIRT-1 and mitigated the hepatic content of MDA, TNF-\u03b1, IL-6, NF-\u03baB, or HIF-1\u03b1 in a dose-dependent manner. Likewise, hepatic photomicrograph stained with hematoxylin and eosin or Masson trichrome stain of EMPA (3 or 6 mg\/kg) revealed marked regression of the hepatotoxic effect of TAA with minimal injury. Similarly, in rats given EMPA (3 or 6 mg\/kg), the immunohistochemically of hepatic photomicrograph revealed minimal stain of either \u03b1-SMA or caspase-3 compared to the TAA group. Therefore, we concluded that EMPA possessed an antifibrotic effect by targeting AMPK\/SIRT-1 activity and inhibiting HIF-1\u03b1. The present study provided new insight into a novel treatment of liver fibrosis.<\/jats:p>","DOI":"10.3390\/antiox11112152","type":"journal-article","created":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:26:50Z","timestamp":1667114810000},"page":"2152","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Effect of Empagliflozin on Thioacetamide-Induced Liver Injury in Rats: Role of AMPK\/SIRT-1\/HIF-1\u03b1 Pathway in Halting Liver Fibrosis"],"prefix":"10.3390","volume":"11","author":[{"given":"Marwan A.","family":"ElBaset","sequence":"first","affiliation":[{"name":"Pharmacology Department, Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo P.O. Box 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4269-0455","authenticated-orcid":false,"given":"Rana S.","family":"Salem","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-5181","authenticated-orcid":false,"given":"Fairouz","family":"Ayman","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-7594","authenticated-orcid":false,"given":"Nadeen","family":"Ayman","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nooran","family":"Shaban","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif M.","family":"Afifi","sequence":"additional","affiliation":[{"name":"Pharmacognosy Department, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2413-6925","authenticated-orcid":false,"given":"Tuba","family":"Esatbeyoglu","sequence":"additional","affiliation":[{"name":"Department of Food Development and Food Quality, Institute of Food Science and Human Nutrition, Gottfried Wilhelm Leibniz University Hannover, Am Kleinen Felde 30, 30167 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6128-3559","authenticated-orcid":false,"given":"Mahmoud","family":"Abdelaziz","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy, October University for Modern Science and Arts, Cairo 12451, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahraa S.","family":"Elalfy","sequence":"additional","affiliation":[{"name":"Pathology Department Medical Research and Clinical Studies Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo P.O. Box 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Roehlen, N., Crouchet, E., and Baumert, T.F. (2020). Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells, 9.","DOI":"10.3390\/cells9040875"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.addr.2017.05.007","article-title":"Hepatic Stellate Cells as Key Target in Liver Fibrosis","volume":"121","author":"Higashi","year":"2017","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8082","DOI":"10.3748\/wjg.v20.i25.8082","article-title":"Oxidative Stress as a Crucial Factor in Liver Diseases","volume":"20","year":"2014","journal-title":"World J. 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