{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T06:07:07Z","timestamp":1776751627819,"version":"3.51.2"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004442","name":"Narodowym Centrum Nauki","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre Poland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.tox.2025.154189","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T15:36:01Z","timestamp":1747064161000},"page":"154189","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Enantiospecific hepatotoxicity of usnic acid in vitro, and the attempt to modify the toxic effect"],"prefix":"10.1016","volume":"516","author":[{"given":"Agnieszka","family":"Galanty","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Pa\u015bko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Koczurkiewicz-Adamczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Siedlarczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"El\u017cbieta","family":"P\u0119kala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irma","family":"Podolak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"23","key":"10.1016\/j.tox.2025.154189_bib1","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1080\/14786419.2015.1007455","article-title":"Review of the biological properties and toxicity of usnic acid","volume":"29","author":"Ara\u00fajo","year":"2015","journal-title":"Nat. Prod. Res."},{"issue":"21","key":"10.1016\/j.tox.2025.154189_bib2","doi-asserted-by":"crossref","first-page":"10909","DOI":"10.3390\/app122110909","article-title":"A look at the importance of chirality in drug activity: Some significative examples","volume":"12","author":"Ceramella","year":"2022","journal-title":"Appl. Sci."},{"issue":"1","key":"10.1016\/j.tox.2025.154189_bib3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/toxsci\/kfu154","article-title":"The role of autophagy in usnic acid-induced toxicity in hepatic cells","volume":"142","author":"Chen","year":"2014","journal-title":"Toxicol. Sci."},{"issue":"1","key":"10.1016\/j.tox.2025.154189_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1081\/GNC-120037931","article-title":"Hepatotoxicity of usnic acid and underlying mechanisms","volume":"43","author":"Chen","year":"2024","journal-title":"J. Environ. Sci. Health C."},{"issue":"1","key":"10.1016\/j.tox.2025.154189_bib5","article-title":"Toxicity of usnic acid: A narrative review","volume":"2022","author":"Croce","year":"2022","journal-title":"J. Toxicol."},{"issue":"2","key":"10.1016\/j.tox.2025.154189_bib6","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ejpb.2006.05.018","article-title":"Nanoencapsulation of usnic acid: an attempt to improve antitumour activity and reduce hepatotoxicity","volume":"64","author":"da Silva Santos","year":"2006","journal-title":"Eur. J. Pharm. Biopharm."},{"issue":"3","key":"10.1016\/j.tox.2025.154189_bib7","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3906\/biy-1609-40","article-title":"Changes in apoptosis-related gene expression profiles in cancer cell lines exposed to usnic acid lichen secondary metabolite","volume":"41","author":"Dincsoy","year":"2017","journal-title":"Turk. J. Biol."},{"issue":"3","key":"10.1016\/j.tox.2025.154189_bib8","first-page":"224","article-title":"Medicinal properties of cinchona alkaloids-a brief review","volume":"11","author":"Dubey","year":"2021","journal-title":"Asian J. Res. Pharm. Sci."},{"issue":"6","key":"10.1016\/j.tox.2025.154189_bib9","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1016\/0031-9422(93)85097-B","article-title":"Toxicity and antifeedant activity of lichen compounds against the polyphagous herbivorous insect Spodoptera littoralis","volume":"33","author":"Emmerich","year":"1993","journal-title":"Phytochemistry"},{"key":"10.1016\/j.tox.2025.154189_bib10","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.tiv.2017.01.008","article-title":"Usnic acid and atranorin exert selective cytostatic and anti-invasive effects on human prostate and melanoma cancer cells","volume":"40","author":"Galanty","year":"2017","journal-title":"Toxicol. Vitr."},{"key":"10.1016\/j.tox.2025.154189_bib11","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s11101-019-09605-3","article-title":"Enantioselective activity of usnic acid: a comprehensive review and future perspectives","volume":"18","author":"Galanty","year":"2019","journal-title":"Phytochem. Rev."},{"issue":"9","key":"10.1016\/j.tox.2025.154189_bib12","doi-asserted-by":"crossref","first-page":"945","DOI":"10.3390\/ph14090945","article-title":"A comparative survey of anti-melanoma and anti-inflammatory potential of usnic acid enantiomers\u2014a comprehensive in vitro approach","volume":"14","author":"Galanty","year":"2021","journal-title":"Pharmaceuticals"},{"issue":"17","key":"10.1016\/j.tox.2025.154189_bib13","doi-asserted-by":"crossref","first-page":"5224","DOI":"10.3390\/molecules26175224","article-title":"+\u2009)-Usnic acid as a promising candidate for a safe and stable topical photoprotective agent","volume":"26","author":"Galanty","year":"2021","journal-title":"Molecules"},{"issue":"7","key":"10.1016\/j.tox.2025.154189_bib14","doi-asserted-by":"crossref","first-page":"806","DOI":"10.3390\/ph15070806","article-title":"In the search for novel, isoflavone-rich functional foods\u2014comparative studies of four clover species sprouts and their chemopreventive potential for breast and prostate cancer","volume":"15","author":"Galanty","year":"2022","journal-title":"Pharmaceuticals"},{"issue":"3","key":"10.1016\/j.tox.2025.154189_bib15","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.bcp.2003.09.032","article-title":"Usnic acid-induced necrosis of cultured mouse hepatocytes: inhibition of mitochondrial function and oxidative stress","volume":"67","author":"Han","year":"2004","journal-title":"Biochem. Pharm."},{"issue":"2","key":"10.1016\/j.tox.2025.154189_bib16","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/j.1600-0536.1993.tb03344.x","article-title":"An investigation of the allergenic constituents of Cladonia stellaris (Opiz) Pous & Ve\u017dda (\u2018silver moss\u2019,\u2018reindeer moss\u2019 or \u2018reindeer lichen\u2019)","volume":"28","author":"Hausen","year":"1993","journal-title":"Contact Dermat."},{"issue":"1","key":"10.1016\/j.tox.2025.154189_bib17","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/toxsci\/kfq026","article-title":"Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification","volume":"115","author":"Jennen","year":"2010","journal-title":"Toxicol. Sci."},{"issue":"12","key":"10.1016\/j.tox.2025.154189_bib18","doi-asserted-by":"crossref","first-page":"6217","DOI":"10.3390\/ijms22126217","article-title":"Cinnamic acid derivatives as cardioprotective agents against oxidative and structural damage induced by doxorubicin","volume":"22","author":"Koczurkiewicz-Adamczyk","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"5-6","key":"10.1016\/j.tox.2025.154189_bib19","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1515\/znc-2014-4178","article-title":"Anti-angiogenic and antiproliferative properties of the lichen substances (-)-usnic acid and vulpinic acid","volume":"70","author":"Koparal","year":"2015","journal-title":"Z. Naturforsch. C."},{"issue":"14","key":"10.1016\/j.tox.2025.154189_bib20","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1080\/14786410601101910","article-title":"In vitro cytotoxic activities of (+)-usnic acid and (\u2212)-usnic acid on V79, A549, and human lymphocyte cells and their non-genotoxicity on human lymphocytes","volume":"20","author":"Koparal","year":"2006","journal-title":"Nat. Prod. Res."},{"issue":"5","key":"10.1016\/j.tox.2025.154189_bib21","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1177\/1091581811414436","article-title":"A metabonomic characterization of (+)-usnic acid-induced liver injury by gas chromatography\u2013mass spectrometry-based metabolic profiling of the plasma and liver in rat","volume":"30","author":"Lu","year":"2011","journal-title":"Int. J. Toxicol."},{"key":"10.1016\/j.tox.2025.154189_bib22","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1007\/s11101-020-09717-1","article-title":"Usnic acid: from an ancient lichen derivative to promising biological and nanotechnology applications","volume":"20","author":"Macedo","year":"2021","journal-title":"Phytochem. Rev."},{"issue":"4","key":"10.1016\/j.tox.2025.154189_bib23","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.3390\/life13041046","article-title":"Critical assessment of the anti-Inflammatory potential of usnic acid and its derivatives\u2014A review","volume":"13","author":"Pa\u017adziora","year":"2023","journal-title":"Life"},{"key":"10.1016\/j.tox.2025.154189_bib24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.fct.2018.07.005","article-title":"Usnic acid reactive metabolites formation in human, rat, and mice microsomes. Implication for hepatotoxicity","volume":"120","author":"Piska","year":"2018","journal-title":"Food Chem. Toxicol."},{"issue":"2-3","key":"10.1016\/j.tox.2025.154189_bib25","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.jep.2003.10.019","article-title":"Hepatotoxic effect of (+) usnic acid from Usnea siamensis Wainio in rats, isolated rat hepatocytes and isolated rat liver mitochondria","volume":"90","author":"Pramyothin","year":"2004","journal-title":"J. Ethnopharm"},{"key":"10.1016\/j.tox.2025.154189_bib26","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1134\/S1990519X17020031","article-title":"Genotoxicity of usnic-acid enantiomers in vitro in human peripheral-blood lymphocytes","volume":"11","author":"Prokopiev","year":"2017","journal-title":"Cell Tissue Biol."},{"issue":"3","key":"10.1016\/j.tox.2025.154189_bib27","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1007\/s10517-018-3979-z","article-title":"Pro\/antigenotoxic activity of usnic acid enantiomers in vitro","volume":"164","author":"Prokopiev","year":"2018","journal-title":"Bull. Exp. Biol. Med."},{"issue":"2-3","key":"10.1016\/j.tox.2025.154189_bib28","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S0014-5793(00)01907-4","article-title":"The phytotoxic lichen metabolite, usnic acid, is a potent inhibitor of plant p-hydroxyphenylpyruvate dioxygenase","volume":"480","author":"Romagni","year":"2000","journal-title":"FEBS Lett."},{"issue":"9","key":"10.1016\/j.tox.2025.154189_bib29","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/jat.1721","article-title":"Effects of usnic acid exposure on human hepatoblastoma HepG2 cells in culture","volume":"32","author":"Sahu","year":"2012","journal-title":"J. Appl. Toxicol."},{"key":"10.1016\/j.tox.2025.154189_bib30","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.876868","article-title":"N-acetylcysteine for the management of non-acetaminophen drug-induced liver injury in adults: a systematic review","volume":"13","author":"Sanabria-Cabrera","year":"2022","journal-title":"Front. Pharm."},{"issue":"14","key":"10.1016\/j.tox.2025.154189_bib31","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.3390\/plants13141985","article-title":"Natural products as hepatoprotective agents\u2014A comprehensive review of clinical trials","volume":"13","author":"S\u0142u\u017ca\u0142y","year":"2024","journal-title":"Plants"},{"issue":"23","key":"10.1016\/j.tox.2025.154189_bib32","doi-asserted-by":"crossref","first-page":"7060","DOI":"10.1016\/j.bmcl.2012.09.084","article-title":"Anti-viral activity of (\u2212)-and (+)-usnic acids and their derivatives against influenza virus A (H1N1) 2009","volume":"22","author":"Sokolov","year":"2012","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"12","key":"10.1016\/j.tox.2025.154189_bib33","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.3390\/cells9122557","article-title":"Characterization of in vitro 3D cell model developed from human hepatocellular carcinoma (HepG2) cell line","volume":"9","author":"\u0160tampar","year":"2020","journal-title":"Cells"},{"issue":"2","key":"10.1016\/j.tox.2025.154189_bib34","doi-asserted-by":"crossref","first-page":"199","DOI":"10.14232\/abs.2020.2.199-206","article-title":"Antioxidant and hepatoprotective property of squalene for counteracting the oxidative damage induced by methotrexate in experimental rats","volume":"64","author":"Sumi","year":"2020","journal-title":"Acta Biol. Szeged"},{"issue":"12","key":"10.1016\/j.tox.2025.154189_bib35","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1080\/14740338.2021.1991307","article-title":"Thalidomide: history, withdrawal, renaissance, and safety concerns","volume":"20","author":"Vargesson","year":"2021","journal-title":"Expert Opin. Drug Saf."},{"issue":"21","key":"10.1016\/j.tox.2025.154189_bib36","doi-asserted-by":"crossref","first-page":"7469","DOI":"10.3390\/molecules27217469","article-title":"Advances in research on bioactivity, toxicity, metabolism, and pharmacokinetics of usnic acid in vitro and in vivo","volume":"27","author":"Wang","year":"2022","journal-title":"Molecules"},{"key":"10.1016\/j.tox.2025.154189_bib37","article-title":"Metabolism and toxicity of usnic acid and barbatic acid based on microsomes, S9 fraction, and 3T3 fibroblasts in vitro combined with a UPLC-Q-TOF-MS method","volume":"14","author":"Wang","year":"2023","journal-title":"Front Pharm."},{"issue":"8","key":"10.1016\/j.tox.2025.154189_bib38","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1248\/cpb.43.1388","article-title":"Screening of tissue cultures and thalli of lichens and some of their active constituents for inhibition of tumor promoter-induced Epstein-Barr virus activation","volume":"43","author":"Yamamoto","year":"1995","journal-title":"Chem. Pharm. Bull."},{"issue":"7","key":"10.1016\/j.tox.2025.154189_bib39","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1111\/jphp.13097","article-title":"Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid","volume":"71","author":"Yurdacan","year":"2019","journal-title":"J. Pharm. Pharm."}],"container-title":["Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25001489?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0300483X25001489?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T06:11:28Z","timestamp":1749017488000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0300483X25001489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":39,"alternative-id":["S0300483X25001489"],"URL":"https:\/\/doi.org\/10.1016\/j.tox.2025.154189","relation":{},"ISSN":["0300-483X"],"issn-type":[{"value":"0300-483X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Enantiospecific hepatotoxicity of usnic acid in vitro, and the attempt to modify the toxic effect","name":"articletitle","label":"Article Title"},{"value":"Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.tox.2025.154189","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"154189"}}