{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:43:59Z","timestamp":1787971439381,"version":"build-2784847793"},"reference-count":57,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Drug\u2010induced liver injury (DILI) is a frequent cause responsible for acute liver failure (ALF). Acetaminophen (APAP) is a known hepatotoxin predictably causing intrinsic DILI. At high doses, APAP causes acute liver necrosis and responsible for ALF and liver transplant cases in 50% and 20% of patients, respectively, in the United States alone. Oxidative stress and glutathione depletion are implicated in APAP\u2010induced liver necrosis. Boldine, a plant\u2010derived compound is shown to have promising antioxidant potential. Therefore, this study investigates the protective effect of boldine against APAP\u2010induced acute hepatic necrosis in mice. A single toxic dose of APAP (300\u2009mg\/kg b.w. p.o.) was administered in overnight\u2010fasted mice to induce acute liver necrosis. Separately, APAP\u2009+\u2009boldine and APAP\u2009+\u2009<jats:italic>N<\/jats:italic>\u2010acetylcysteine (NAC) simultaneous treatments were also given. Serum transaminases and reduced glutathione, enzymic antioxidants, tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interleukin\u20101\u03b2 (IL\u20101\u03b2), and, IL\u20106 were evaluated in liver tissue. Acute APAP intoxication significantly elevated serum marker enzymes of hepatotoxicity. APAP administration increased lipid peroxidation, TNF\u2010\u03b1, IL\u20101\u03b2, and IL\u20106 protein expressions. The enzymic antioxidants and reduced glutathione levels were decreased in liver tissue of APAP intoxicated mice. Boldine and NAC simultaneous treatments prevented APAP\u2010induced oxidative stress, inflammation, and necrosis. The results of this study suggest the crucial role of boldine to protect against APAP induced hepatotoxicity by virtue of its antioxidant and anti\u2010inflammatory properties.<\/jats:p>","DOI":"10.1002\/jbt.22697","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T12:17:15Z","timestamp":1609762635000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Boldine treatment protects acetaminophen\u2010induced liver inflammation and acute hepatic necrosis in mice"],"prefix":"10.1002","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5068-2383","authenticated-orcid":false,"given":"Devaraj","family":"Ezhilarasan","sequence":"first","affiliation":[{"name":"Department of Pharmacology,\u00a0The Blue Lab (Molecular Pharmacology and Toxicology Division), Saveetha Dental College Saveetha Institute of Medical and Technical Sciences  Chennai Tamil Nadu India"},{"name":"Department of Pharmacology, Biomedical Research Unit and Laboratory Animal Centre, Saveetha Dental College Saveetha Institute of Medical and Technical Sciences  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramanian","family":"Raghunandhakumar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology,\u00a0The Blue Lab (Molecular Pharmacology and Toxicology Division), Saveetha Dental College Saveetha Institute of Medical and Technical Sciences  Chennai Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2015.12.017"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-020-02885-1"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.287"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1816149"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.01092"},{"key":"e_1_2_8_7_1","volume-title":"Acetaminophen (paracetamol) poisoning in adults: Pathophysiology, presentation, and diagnosis","author":"Burns M. J.","year":"2017"},{"issue":"2","key":"e_1_2_8_8_1","first-page":"131","volume":"4","author":"Yoon E.","year":"2016","journal-title":"J. Clin. Transl. Hepatol"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2016.08.007"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1679919"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.02.006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.34857"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.11622\/smedj.2016170"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2018.04.019"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.5811\/westjem.2012.4.6885"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.11.033"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i42.7440"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2016.20.1.15"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1211\/jpp.62.05.0012"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2005.09.002"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000185"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0043-113447"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/a-0659-2478"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22404"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phanu.2017.07.001"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4103\/0974-8490.112417"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.15171\/PS.2019.1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1177\/0023677215570992"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfg181"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/28.1.56"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(79)90738-3"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1974.tb03714.x"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(72)90132-7"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_8_35_1","first-page":"882","volume":"61","author":"Beutler E.","year":"1963","journal-title":"J. Lab. Clin. Med"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)42083-8"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.179.4073.588"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)83745-6"},{"key":"e_1_2_8_39_1","first-page":"49","volume-title":"Manual of Histological Techniques","author":"Bancroft J. D.","year":"1984"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19123776"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00509"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-01810-8"},{"key":"e_1_2_8_43_1","first-page":"303","volume":"6","author":"Hepatoprotective W. R.","year":"2016","journal-title":"Front. Pharmacol"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6503"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191353"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.4103\/abr.abr_142_17"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfda.2016.03.002"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2012.08.015"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.3727\/105221617X15084371374138"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajg.2018.03.002"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201708007"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.indcrop.2013.11.051"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-00663-0_12"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI59755"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2017.01.004"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00705"},{"issue":"6","key":"e_1_2_8_57_1","first-page":"331","volume":"3","author":"Krenkel O.","year":"2014","journal-title":"Hepatobiliary Surg. Nutr"},{"key":"e_1_2_8_58_1","first-page":"630265","author":"Tsutsui H.","year":"2015","journal-title":"Mediators\u00a0Inflamm"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22697","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.22697","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.22697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T04:56:00Z","timestamp":1693630560000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.22697"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,4]]},"references-count":57,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1002\/jbt.22697"],"URL":"https:\/\/doi.org\/10.1002\/jbt.22697","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,4]]},"assertion":[{"value":"2020-06-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22697"}}