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In this study, we evaluated the effects of \u03b2\u2010lapachone (\u03b2\u2010LAP),\u00a0a natural quinone\u2010containing compound, in a mouse model of DOX\u2010induced hepatotoxicity. \u03b2\u2010LAP\u00a0was orally administered at 1.25, 2.5, and 5\u2009mg\/kg for 4 days, and a single dose of DOX (20\u2009mg\/kg) was injected intraperitoneally on the second day. Histopathological changes, liver function markers, antioxidant and inflammatory markers were assessed. \u03b2\u2010LAP\u00a0ameliorated liver injury and liver function markers evoked by DOX. \u03b2\u2010LAP also downregulated the mRNA expression of nuclear factor\u2010kB\u2010corresponding genes including interleukin\u20106, interleukin\u20101\u03b2, and tumor necrosis factor\u2010\u03b1. Moreover, \u03b2\u2010LAP\u00a0increased the nuclear factor erythroid 2\u2010related factor 2 target genes heme oxygenase\u20101 and NAD(P)H: quinone oxidoreductase 1, along with antioxidant enzymes including reduced glutathione, catalase, and superoxide dismutase with simultaneous reduction in the lipid peroxidation product malondialdehyde. Meanwhile, it recovered NAD<jats:sup>+<\/jats:sup>\/NADH ratios and subsequently elevated the protein levels of sirtuin\u20101 (SIRT\u20101),\u00a0farnesoid X receptor (FXR),\u00a0and phosphorylated AMP\u2010activated protein kinase (p\u2010AMPK).\u00a0Collectively, these findings suggest a protective role of \u03b2\u2010LAP\u00a0against DOX\u2010induced hepatotoxicity by partly regulating the NAD<jats:sup>+<\/jats:sup>\/SIRT\u20101\/FXR\/p\u2010AMPK\u00a0axis.<\/jats:p>","DOI":"10.1002\/jbt.23564","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T04:00:19Z","timestamp":1698033619000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["\u03b2\u2010lapachone protects against doxorubicin\u2010induced hepatotoxicity through modulation of NAD<sup>+<\/sup>\/SIRT\u20101\/FXR\/p\u2010AMPK\/NF\u2010kB and Nrf2 signaling axis"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-3147","authenticated-orcid":false,"given":"Ashkan","family":"Kalantary\u2010Charvadeh","sequence":"first","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine Hamadan University of Medical Sciences Hamadan Iran"},{"name":"Student Research Committee Hamadan University of Medical Sciences Hamadan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saeed","family":"Nazari Soltan Ahmad","sequence":"additional","affiliation":[{"name":"Drug Applied Research Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Somayeh","family":"Aslani","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine Hamadan University of Medical Sciences Hamadan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Beyrami","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine Hamadan University of Medical Sciences Hamadan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehran","family":"Mesgari\u2010Abbasi","sequence":"additional","affiliation":[{"name":"Drug Applied Research Center Tabriz University of Medical Sciences Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117599"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2020.153402"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.03.023"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2019.02.013"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111708"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-019-09511-2"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112594"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.4149\/BLL_2017_054"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.09.001"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10121998"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jksus.2021.101640"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01030"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2021.112713"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.07.057"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.05.024"},{"issue":"2","key":"e_1_2_10_17_1","first-page":"17","volume":"5","author":"Nikkhah S.","year":"2021","journal-title":"Genet. 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