{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T22:06:58Z","timestamp":1782338818442,"version":"3.54.5"},"reference-count":62,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Plovdiv","award":["NO-03\/2023"],"award-info":[{"award-number":["NO-03\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acetaminophen (APAP) overdose can result in potentially fatal acute liver failure, with free radical formation identified as a major mechanism of liver tissue damage. Micromeria frivaldszkyana (M. frivaldszkyana), a rare species endemic to Bulgaria, has demonstrated significant antioxidant activity. Male Wistar rats were treated orally for 7 days with saline; 250, 400, or 500 mg\/kg of a water solution of dried methanolic extract of M. frivaldszkyana; 100 mg\/kg rosmarinic acid (RA); or 125 mg\/kg silymarin. Liver toxicity was induced by oral application of 2000 mg\/kg APAP on the last day of treatment. Forty-eight hours later, blood and livers were collected for histological and biochemical analysis. The results revealed that treatment with 500 mg\/kg of the dried methanolic extract significantly reduced the elevated levels of aspartate aminotransferase, alanine aminotransferase, malondialdehyde, 8-hydroxy-2\u2032-deoxyguanosine, and tumor necrosis factor-alpha in APAP overdose. The present results clearly demonstrate, for the first time, that pre-treatment with methanolic extract of M. frivaldszkyana results in significant hepatoprotective effects in the APAP-induced rat model of liver injury. The mechanism of this effect may involve cell membrane protection, decreased lipid peroxidation and DNA damage, and attenuation of aseptic inflammation. These effects can be attributed to the main compounds identified in the extract (linarin, chlorogenic acid, rutin, eupatorin, apigenin, RA).<\/jats:p>","DOI":"10.3390\/ijms26189112","type":"journal-article","created":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T14:45:46Z","timestamp":1758206746000},"page":"9112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Protective Effects of Methanolic Extract of Micromeria frivaldszkyana (Degen) Velen Against Acetaminophen-Induced Liver Toxicity in Male Wistar Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5167-3278","authenticated-orcid":false,"given":"Elisaveta","family":"Apostolova","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacotherapy, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6640-8617","authenticated-orcid":false,"given":"Kristina","family":"Stavrakeva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacotherapy, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5578-7862","authenticated-orcid":false,"given":"Vesela","family":"Kokova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology, and Pharmacotherapy, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"},{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8406-1446","authenticated-orcid":false,"given":"Ivica","family":"Dimov","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5489-8106","authenticated-orcid":false,"given":"Mariya","family":"Choneva","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3695-5688","authenticated-orcid":false,"given":"Delyan","family":"Delev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2397-0988","authenticated-orcid":false,"given":"Ilia","family":"Kostadinov","sequence":"additional","affiliation":[{"name":"Research Institute, Medical University of Plovdiv, 4002 Plovdiv, Bulgaria"},{"name":"Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilia","family":"Bivolarski","sequence":"additional","affiliation":[{"name":"Department of General and Clinical Pathology, Faculty of Medicine, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Koleva","sequence":"additional","affiliation":[{"name":"Department of General and Clinical Pathology, Faculty of Medicine, Medical University of Plovdiv, 4000 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumen","family":"Mladenov","sequence":"additional","affiliation":[{"name":"Department of Botany and Biological Education, Faculty of Biology, University of Plovdiv \u201cPaisii Hilendarski\u201d, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"},{"name":"Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-1444","authenticated-orcid":false,"given":"Plamen","family":"Stoyanov","sequence":"additional","affiliation":[{"name":"Department of Botany and Biological Education, Faculty of Biology, University of Plovdiv \u201cPaisii Hilendarski\u201d, 24 Tsar Assen Str., 4000 Plovdiv, Bulgaria"},{"name":"Department of Bioorganic Chemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2157-3858","authenticated-orcid":false,"given":"Anelia","family":"Bivolarska","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Faculty of Pharmacy, Medical University of Plovdiv, Vasil Aprilov Str. 15A, 4002 Plovdiv, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dkhil, M.A., Abdel Moneim, A.E., Hafez, T.A., Mubaraki, M.A., Mohamed, W.F., Thagfan, F.A., and Al-Quraishy, S. 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