{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T12:40:17Z","timestamp":1791895217109,"version":"4.3.4"},"reference-count":161,"publisher":"Elsevier BV","issue":"8","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["dmd.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Drug Metabolism and Disposition"],"published-print":{"date-parts":[[2024,8]]},"DOI":"10.1124\/dmd.123.001279","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T12:10:27Z","timestamp":1721131827000},"page":"712-721","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":49,"title":["Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress"],"prefix":"10.1016","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8695-6980","authenticated-orcid":false,"given":"Hartmut","family":"Jaeschke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5438-2409","authenticated-orcid":false,"given":"Anup","family":"Ramachandran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/dmd.123.001279_bib1","doi-asserted-by":"crossref","first-page":"116043","DOI":"10.1016\/j.taap.2022.116043","article-title":"The role of Iron in lipid peroxidation and protein nitration during acetaminophen-induced liver injury in mice","volume":"445","author":"Adelusi","year":"2022","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1124\/jpet.111.184192","article-title":"Acetaminophen-induced hepatotoxicity and protein nitration in neuronal nitric-oxide synthase knockout mice","volume":"340","author":"Agarwal","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib3","doi-asserted-by":"crossref","first-page":"3377","DOI":"10.1007\/s00204-021-03142-9","article-title":"Delayed administration of N-acetylcysteine blunts recovery after an acetaminophen overdose unlike 4-methylpyrazole","volume":"95","author":"Akakpo","year":"2021","journal-title":"Arch Toxicol"},{"key":"10.1124\/dmd.123.001279_bib4","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1007\/s00204-021-03211-z","article-title":"Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for acetaminophen overdose","volume":"96","author":"Akakpo","year":"2022","journal-title":"Arch Toxicol"},{"key":"10.1124\/dmd.123.001279_bib5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/toxsci\/kfz077","article-title":"Delayed treatment with 4-methylpyrazole protects against acetaminophen hepatotoxicity in mice by inhibition of c-jun N-terminal kinase","volume":"170","author":"Akakpo","year":"2019","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib6","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1177\/0960327118774902","article-title":"4-Methylpyrazole protects against acetaminophen hepatotoxicity in mice and in primary human hepatocytes","volume":"37","author":"Akakpo","year":"2018","journal-title":"Hum Exp Toxicol"},{"key":"10.1124\/dmd.123.001279_bib7","doi-asserted-by":"crossref","first-page":"115317","DOI":"10.1016\/j.taap.2020.115317","article-title":"4-methylpyrazole protects against acetaminophen-induced acute kidney injury","volume":"409","author":"Akakpo","year":"2020","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib8","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1080\/01926230701311344","article-title":"Emerging role of Nrf2 in protecting against hepatic and gastrointestinal disease","volume":"35","author":"Aleksunes","year":"2007","journal-title":"Toxicol Pathol"},{"key":"10.1124\/dmd.123.001279_bib9","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1124\/dmd.105.006759","article-title":"Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells","volume":"34","author":"Aninat","year":"2006","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.123.001279_bib10","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1002\/hep.26294","article-title":"Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital","volume":"58","author":"Antoine","year":"2013","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib11","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1093\/toxsci\/kfl077","article-title":"Nuclear translocation of endonuclease G and apoptosis-inducing factor during acetaminophen-induced liver cell injury","volume":"94","author":"Bajt","year":"2006","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib12","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1124\/jpet.107.129445","article-title":"Mitochondrial bax translocation accelerates DNA fragmentation and cell necrosis in a murine model of acetaminophen hepatotoxicity","volume":"324","author":"Bajt","year":"2008","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib13","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/toxsci\/kfh151","article-title":"Acetaminophen-induced oxidant stress and cell injury in cultured mouse hepatocytes: protection by N-acetyl cysteine","volume":"80","author":"Bajt","year":"2004","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib14","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1093\/toxsci\/kfr116","article-title":"Apoptosis-inducing factor modulates mitochondrial oxidant stress in acetaminophen hepatotoxicity","volume":"122","author":"Bajt","year":"2011","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib15","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.toxrep.2017.02.005","article-title":"Trifluoperazine inhibits acetaminophen-induced hepatotoxicity and hepatic reactive nitrogen formation in mice and in freshly isolated hepatocytes","volume":"4","author":"Banerjee","year":"2017","journal-title":"Toxicol Rep"},{"key":"10.1124\/dmd.123.001279_bib16","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.freeradbiomed.2015.09.022","article-title":"The neuronal nitric oxide synthase inhibitor NANT blocks acetaminophen toxicity and protein nitration in freshly isolated hepatocytes","volume":"89","author":"Banerjee","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"10.1124\/dmd.123.001279_bib17","doi-asserted-by":"crossref","first-page":"424","DOI":"10.3109\/15563650.2010.486381","article-title":"A multicenter comparison of the safety of oral versus intravenous acetylcysteine for treatment of acetaminophen overdose","volume":"48","author":"Bebarta","year":"2010","journal-title":"Clin Toxicol (Phila)"},{"key":"10.1124\/dmd.123.001279_bib18","doi-asserted-by":"crossref","first-page":"147","DOI":"10.2217\/bmm.13.150","article-title":"Targeted liquid chromatography-mass spectrometry analysis of serum acylcarnitines in acetaminophen toxicity in children","volume":"8","author":"Bhattacharyya","year":"2014","journal-title":"Biomarkers Med"},{"key":"10.1124\/dmd.123.001279_bib19","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.ajpath.2018.12.006","article-title":"Liver Regeneration after Acetaminophen Hepatotoxicity: Mechanisms and Therapeutic Opportunities","volume":"189","author":"Bhushan","year":"2019","journal-title":"Am J Pathol"},{"key":"10.1124\/dmd.123.001279_bib20","doi-asserted-by":"crossref","first-page":"115","DOI":"10.3727\/105221618X15205260749346","article-title":"DNA Damage Response Regulates Initiation of Liver Regeneration Following Acetaminophen Overdose","volume":"18","author":"Borude","year":"2018","journal-title":"Gene Expr"},{"key":"10.1124\/dmd.123.001279_bib21","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1021\/tx1001755","article-title":"Reactive nitrogen species in acetaminophen-induced mitochondrial damage and toxicity in mouse hepatocytes","volume":"23","author":"Burke","year":"2010","journal-title":"Chem Res Toxicol"},{"key":"10.1124\/dmd.123.001279_bib22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1179\/1351000214Y.0000000099","article-title":"Metal-catalyzed protein tyrosine nitration in biological systems","volume":"19","author":"Campolo","year":"2014","journal-title":"Redox Rep"},{"key":"10.1124\/dmd.123.001279_bib23","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.1073\/pnas.081082098","article-title":"An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen","volume":"98","author":"Chan","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/dmd.123.001279_bib24","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1111\/liv.13866","article-title":"Role and mechanisms of autophagy in acetaminophen-induced liver injury","volume":"38","author":"Chao","year":"2018","journal-title":"Liver Int"},{"key":"10.1124\/dmd.123.001279_bib25","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1124\/dmd.104.002402","article-title":"The cyp2e1-humanized transgenic mouse: role of cyp2e1 in acetaminophen hepatotoxicity","volume":"33","author":"Cheung","year":"2005","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.123.001279_bib26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/taap.1996.8074","article-title":"Selective protein covalent binding and target organ toxicity","volume":"143","author":"Cohen","year":"1997","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib27","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/S0022-3565(25)20924-7","article-title":"Effects of N-acetylcysteine on acetaminophen covalent binding and hepatic necrosis in mice","volume":"232","author":"Corcoran","year":"1985","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib28","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0022-3565(25)20923-5","article-title":"Effects of N-acetylcysteine on the disposition and metabolism of acetaminophen in mice","volume":"232","author":"Corcoran","year":"1985","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib29","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/S0022-3565(25)25048-0","article-title":"Role of glutathione in prevention of acetaminophen-induced hepatotoxicity by N-acetyl-L-cysteine in vivo: studies with N-acetyl-D-cysteine in mice","volume":"238","author":"Corcoran","year":"1986","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib30","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1124\/jpet.105.088898","article-title":"Peroxynitrite-induced mitochondrial and endonuclease-mediated nuclear DNA damage in acetaminophen hepatotoxicity","volume":"315","author":"Cover","year":"2005","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib31","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1073\/pnas.81.5.1327","article-title":"N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen","volume":"81","author":"Dahlin","year":"1984","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/dmd.123.001279_bib32","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1053\/j.gastro.2006.01.033","article-title":"Measurement of serum acetaminophen-protein adducts in patients with acute liver failure","volume":"130","author":"Davern","year":"2006","journal-title":"Gastroenterology"},{"key":"10.1124\/dmd.123.001279_bib33","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1136\/bmj.2.5512.497","article-title":"Acute liver necrosis following overdose of paracetamol","volume":"2","author":"Davidson","year":"1966","journal-title":"BMJ"},{"key":"10.1124\/dmd.123.001279_bib34","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/bcp.15596","article-title":"Fomepizole should not be used more liberally in paracetamol overdose","volume":"89","author":"Dear","year":"2023","journal-title":"Br J Clin Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib35","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s00204-016-1692-0","article-title":"Mitochondria-targeted antioxidant Mito-Tempo protects against acetaminophen hepatotoxicity","volume":"91","author":"Du","year":"2017","journal-title":"Arch Toxicol"},{"key":"10.1124\/dmd.123.001279_bib36","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.redox.2016.10.001","article-title":"Oxidative stress during acetaminophen hepatotoxicity: Sources, pathophysiological role and therapeutic potential","volume":"10","author":"Du","year":"2016","journal-title":"Redox Biol"},{"issue":"Pt A","key":"10.1124\/dmd.123.001279_bib37","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.fct.2017.08.020","article-title":"Induction of mitochondrial biogenesis protects against acetaminophen hepatotoxicity","volume":"108","author":"Du","year":"2017","journal-title":"Food Chem Toxicol"},{"key":"10.1124\/dmd.123.001279_bib38","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/toxsci\/kfw158","article-title":"Editor\u2019s Highlight: Metformin Protects Against Acetaminophen Hepatotoxicity by Attenuation of Mitochondrial Oxidant Stress and Dysfunction","volume":"154","author":"Du","year":"2016","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib39","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1007\/s00204-018-2331-8","article-title":"Mito-tempo protects against acute liver injury but induces limited secondary apoptosis during the late phase of acetaminophen hepatotoxicity","volume":"93","author":"Du","year":"2019","journal-title":"Arch Toxicol"},{"key":"10.1124\/dmd.123.001279_bib40","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.taap.2014.09.002","article-title":"Lower susceptibility of female mice to acetaminophen hepatotoxicity: Role of mitochondrial glutathione, oxidant stress and c-jun N-terminal kinase","volume":"281","author":"Du","year":"2014","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib41","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/toxsci\/59.1.169","article-title":"High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes","volume":"59","author":"Enomoto","year":"2001","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib42","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1111\/bcp.15594","article-title":"Fomepizole should be used more liberally in paracetamol overdose","volume":"89","author":"Filip","year":"2023","journal-title":"Br J Clin Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib43","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1177\/0192623308329282","article-title":"Sensitivity of liver injury in heterozygous Sod2 knockout mice treated with troglitazone or acetaminophen","volume":"37","author":"Fujimoto","year":"2009","journal-title":"Toxicol Pathol"},{"key":"10.1124\/dmd.123.001279_bib44","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1002\/hep.510270316","article-title":"Role of nitric oxide in acetaminophen-induced hepatotoxicity in the rat","volume":"27","author":"Gardner","year":"1998","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib45","first-page":"1465","article-title":"In situ detection of fragmented DNA (TUNEL assay) fails to discriminate among apoptosis, necrosis, and autolytic cell death: a cautionary note","volume":"21","author":"Grasl-Kraupp","year":"1995","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib46","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1093\/toxsci\/67.2.322","article-title":"Mode of cell death after acetaminophen overdose in mice: apoptosis or oncotic necrosis?","volume":"67","author":"Gujral","year":"2002","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib47","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1053\/j.gastro.2006.03.045","article-title":"c-Jun N-terminal kinase plays a major role in murine acetaminophen hepatotoxicity","volume":"131","author":"Gunawan","year":"2006","journal-title":"Gastroenterology"},{"key":"10.1124\/dmd.123.001279_bib48","doi-asserted-by":"crossref","first-page":"13565","DOI":"10.1074\/jbc.M708916200","article-title":"Role of JNK translocation to mitochondria leading to inhibition of mitochondria bioenergetics in acetaminophen-induced liver injury","volume":"283","author":"Hanawa","year":"2008","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.123.001279_bib49","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1006\/bbrc.2002.6541","article-title":"Reduction of toxic metabolite formation of acetaminophen","volume":"291","author":"Hazai","year":"2002","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1124\/dmd.123.001279_bib50","doi-asserted-by":"crossref","first-page":"116452","DOI":"10.1016\/j.taap.2023.116452","article-title":"Mitoquinone protects against acetaminophen-induced liver injury in an FSP1-dependent and GPX4-independent manner","volume":"465","author":"He","year":"2023","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib51","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1111\/bcp.12831","article-title":"Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing","volume":"81","author":"Heard","year":"2016","journal-title":"Br J Clin Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib52","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.freeradbiomed.2016.06.024","article-title":"Translocation of iron from lysosomes to mitochondria during acetaminophen-induced hepatocellular injury: Protection by starch-desferal and minocycline","volume":"97","author":"Hu","year":"2016","journal-title":"Free Radic Biol Med"},{"key":"10.1124\/dmd.123.001279_bib53","doi-asserted-by":"crossref","first-page":"114930","DOI":"10.1016\/j.taap.2020.114930","article-title":"Suppression of iron mobilization from lysosomes to mitochondria attenuates liver injury after acetaminophen overdose in vivo in mice: Protection by minocycline","volume":"392","author":"Hu","year":"2020","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib54","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1006\/niox.2001.0404","article-title":"Effect of inhibitors of nitric oxide synthase on acetaminophen-induced hepatotoxicity in mice","volume":"6","author":"Hinson","year":"2002","journal-title":"Nitric Oxide"},{"key":"10.1124\/dmd.123.001279_bib55","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1021\/tx9800349","article-title":"Nitrotyrosine-protein adducts in hepatic centrilobular areas following toxic doses of acetaminophen in mice","volume":"11","author":"Hinson","year":"1998","journal-title":"Chem Res Toxicol"},{"key":"10.1124\/dmd.123.001279_bib56","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S0022-3565(25)23217-7","article-title":"Glutathione disulfide formation and oxidant stress during acetaminophen-induced hepatotoxicity in mice in vivo: the protective effect of allopurinol","volume":"255","author":"Jaeschke","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib57","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1159\/000374090","article-title":"Acetaminophen: Dose-Dependent Drug Hepatotoxicity and Acute Liver Failure in Patients","volume":"33","author":"Jaeschke","year":"2015","journal-title":"Dig Dis"},{"key":"10.1124\/dmd.123.001279_bib58","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3727\/105221621X16104581979144","article-title":"Ferroptosis and Acetaminophen Hepatotoxicity: Are We Going Down Another Rabbit Hole?","volume":"20","author":"Jaeschke","year":"2021","journal-title":"Gene Expr"},{"key":"10.1124\/dmd.123.001279_bib59","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.fct.2018.06.025","article-title":"The role of apoptosis in acetaminophen hepatotoxicity","volume":"118","author":"Jaeschke","year":"2018","journal-title":"Food Chem Toxicol"},{"key":"10.1124\/dmd.123.001279_bib60","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.livres.2019.10.002","article-title":"Mitochondrial Damage and Biogenesis in Acetaminophen-induced Liver Injury","volume":"3","author":"Jaeschke","year":"2019","journal-title":"Liver Res"},{"key":"10.1124\/dmd.123.001279_bib61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0378-4274(03)00239-X","article-title":"The role of oxidant stress and reactive nitrogen species in acetaminophen hepatotoxicity","volume":"144","author":"Jaeschke","year":"2003","journal-title":"Toxicol Lett"},{"key":"10.1124\/dmd.123.001279_bib62","series-title":"McQueen CA, Comprehensive Toxicology, Vol. 2","first-page":"277","article-title":"Antioxidant defense mechanisms","author":"Jaeschke","year":"2018"},{"key":"10.1124\/dmd.123.001279_bib63","doi-asserted-by":"crossref","first-page":"111240","DOI":"10.1016\/j.fct.2020.111240","article-title":"Mechanisms and pathophysiological significance of sterile inflammation during acetaminophen hepatotoxicity","volume":"138","author":"Jaeschke","year":"2020","journal-title":"Food Chem Toxicol"},{"key":"10.1124\/dmd.123.001279_bib64","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/hep.23940","article-title":"No evidence for caspase-dependent apoptosis in acetaminophen hepatotoxicity","volume":"53","author":"Jaeschke","year":"2011","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib65","first-page":"1659","article-title":"DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells","volume":"61","author":"Jahr","year":"2001","journal-title":"Cancer Res"},{"key":"10.1124\/dmd.123.001279_bib66","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1093\/toxsci\/kfg181","article-title":"Effect of N-acetylcysteine on acetaminophen toxicity in mice: relationship to reactive nitrogen and cytokine formation","volume":"75","author":"James","year":"2003","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib67","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0022-3565(25)29664-1","article-title":"Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo","volume":"187","author":"Jollow","year":"1973","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib68","doi-asserted-by":"crossref","first-page":"14126","DOI":"10.1073\/pnas.241380298","article-title":"Identification of a neuronal nitric oxide synthase in isolated cardiac mitochondria using electrochemical detection","volume":"98","author":"Kanai","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/dmd.123.001279_bib69","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1007\/s13181-019-00740-z","article-title":"The Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers","volume":"16","author":"Kang","year":"2020","journal-title":"J Med Toxicol"},{"key":"10.1124\/dmd.123.001279_bib70","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/s12276-023-00965-7","article-title":"Molecular mechanisms of mitochondrial DNA release and activation of the cGAS-STING pathway","volume":"55","author":"Kim","year":"2023","journal-title":"Exp Mol Med"},{"key":"10.1124\/dmd.123.001279_bib71","doi-asserted-by":"crossref","first-page":"104892","DOI":"10.1016\/j.yrtph.2021.104892","article-title":"A comprehensive weight of evidence assessment of published acetaminophen genotoxicity data: Implications for its carcinogenic hazard potential","volume":"122","author":"Kirkland","year":"2021","journal-title":"Regul Toxicol Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib72","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.taap.2010.01.013","article-title":"Nrf2 the rescue: effects of the antioxidative\/electrophilic response on the liver","volume":"244","author":"Klaassen","year":"2010","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib73","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/toxsci\/kfg220","article-title":"Role of lipid peroxidation as a mechanism of liver injury after acetaminophen overdose in mice","volume":"76","author":"Knight","year":"2003","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib74","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1124\/jpet.102.038968","article-title":"Peroxynitrite is a critical mediator of acetaminophen hepatotoxicity in murine livers: protection by glutathione","volume":"303","author":"Knight","year":"2002","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib75","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/toxsci\/62.2.212","article-title":"Vascular and hepatocellular peroxynitrite formation during acetaminophen toxicity: role of mitochondrial oxidant stress","volume":"62","author":"Knight","year":"2001","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib76","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1002\/hep.20437","article-title":"Mitochondrial permeability transition in acetaminophen-induced necrosis and apoptosis of cultured mouse hepatocytes","volume":"40","author":"Kon","year":"2004","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib77","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1093\/toxsci\/kfq175","article-title":"Lysosomal iron mobilization and induction of the mitochondrial permeability transition in acetaminophen-induced toxicity to mouse hepatocytes","volume":"117","author":"Kon","year":"2010","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib78","article-title":"The Role of Carbamoyl Phosphate Synthetase 1 as a Prognostic Biomarker in Patients With Acetaminophen-induced Acute Liver Failure","volume":"27","author":"Kwan","year":"2023","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1124\/dmd.123.001279_bib79","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.2741\/3539","article-title":"Mitochondrial nitric oxide synthase: current concepts and controversies","volume":"14","author":"Lacza","year":"2009","journal-title":"Front Biosci"},{"key":"10.1124\/dmd.123.001279_bib80","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/S0891-5849(03)00510-0","article-title":"Mitochondrial nitric oxide synthase is not eNOS, nNOS or iNOS","volume":"35","author":"Lacza","year":"2003","journal-title":"Free Radic Biol Med"},{"key":"10.1124\/dmd.123.001279_bib81","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.cld.2007.06.006","article-title":"Acetaminophen hepatotoxicity","volume":"11","author":"Larson","year":"2007","journal-title":"Clin Liver Dis"},{"key":"10.1124\/dmd.123.001279_bib82","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1006\/taap.1999.8635","article-title":"Inhibition of Fas receptor (CD95)-induced hepatic caspase activation and apoptosis by acetaminophen in mice","volume":"156","author":"Lawson","year":"1999","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib83","doi-asserted-by":"crossref","first-page":"12063","DOI":"10.1074\/jbc.271.20.12063","article-title":"Role of CYP2E1 in the hepatotoxicity of acetaminophen","volume":"271","author":"Lee","year":"1996","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.123.001279_bib84","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1042\/bj20031049","article-title":"Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products","volume":"378","author":"Levonen","year":"2004","journal-title":"Biochem J"},{"key":"10.1124\/dmd.123.001279_bib85","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1016\/j.jhep.2014.05.033","article-title":"Adiponectin protects against acetaminophen-induced mitochondrial dysfunction and acute liver injury by promoting autophagy in mice","volume":"61","author":"Lin","year":"2014","journal-title":"J Hepatol"},{"key":"10.1124\/dmd.123.001279_bib86","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/0014-5793(74)80281-4","article-title":"Superoxide radicals as precursors of mitochondrial hydrogen peroxide","volume":"42","author":"Loschen","year":"1974","journal-title":"FEBS Lett"},{"key":"10.1124\/dmd.123.001279_bib87","article-title":"Immune and inflammatory cell engagement in acetaminophen-induced liver injury and repair.","author":"Luyendyk","year":"2023","journal-title":"Drug Metab Dispos"},{"key":"10.1124\/dmd.123.001279_bib88","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/j.1742-7843.2004.pto940504.x","article-title":"N-acetylcysteine does not protect HepG2 cells against acetaminophen-induced apoptosis","volume":"94","author":"Manov","year":"2004","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1124\/dmd.123.001279_bib89","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1111\/bcp.13214","article-title":"Outcomes from massive paracetamol overdose: a retrospective observational study","volume":"83","author":"Marks","year":"2017","journal-title":"Br J Clin Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib90","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1007\/s10495-019-01571-7","article-title":"Liver-specific Bid silencing inhibits APAP-induced cell death in mice","volume":"24","author":"Maxa","year":"2019","journal-title":"Apoptosis"},{"key":"10.1124\/dmd.123.001279_bib91","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s00204-013-1118-1","article-title":"Circulating acylcarnitines as biomarkers of mitochondrial dysfunction after acetaminophen overdose in mice and humans","volume":"88","author":"McGill","year":"2014","journal-title":"Arch Toxicol"},{"key":"10.1124\/dmd.123.001279_bib92","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1172\/JCI59755","article-title":"The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation","volume":"122","author":"McGill","year":"2012","journal-title":"J Clin Invest"},{"key":"10.1124\/dmd.123.001279_bib93","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/hep.27265","article-title":"Serum mitochondrial biomarkers and damage-associated molecular patterns are higher in acetaminophen overdose patients with poor outcome","volume":"60","author":"McGill","year":"2014","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib94","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.taap.2012.08.015","article-title":"Acetaminophen-induced liver injury in rats and mice: comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity","volume":"264","author":"McGill","year":"2012","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib95","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1002\/hep.24132","article-title":"HepaRG cells: a human model to study mechanisms of acetaminophen hepatotoxicity","volume":"53","author":"McGill","year":"2011","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib96","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1038\/clpt.2010.157","article-title":"Antidotes for alcohol and glycol toxicity: translating mechanisms into treatments","volume":"88","author":"McMartin","year":"2010","journal-title":"Clin Pharmacol Ther"},{"key":"10.1124\/dmd.123.001279_bib97","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/0041-008X(88)90040-3","article-title":"Acetaminophen-induced inhibition of hepatic mitochondrial respiration in mice","volume":"93","author":"Meyers","year":"1988","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib98","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1006\/niox.2001.0385","article-title":"Acetaminophen-induced hepatotoxicity in mice lacking inducible nitric oxide synthase activity","volume":"5","author":"Michael","year":"2001","journal-title":"Nitric Oxide"},{"key":"10.1124\/dmd.123.001279_bib99","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S0022-3565(25)29663-X","article-title":"Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism","volume":"187","author":"Mitchell","year":"1973","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib100","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0022-3565(25)29666-5","article-title":"Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione","volume":"187","author":"Mitchell","year":"1973","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib101","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1146\/annurev.immunol.23.021704.115811","article-title":"DNA degradation in development and programmed cell death","volume":"23","author":"Nagata","year":"2005","journal-title":"Annu Rev Immunol"},{"key":"10.1124\/dmd.123.001279_bib102","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1053\/j.gastro.2008.07.006","article-title":"Deletion of apoptosis signal-regulating kinase 1 attenuates acetaminophen-induced liver injury by inhibiting c-Jun N-terminal kinase activation","volume":"135","author":"Nakagawa","year":"2008","journal-title":"Gastroenterology"},{"key":"10.1124\/dmd.123.001279_bib103","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1111\/bcpt.12631","article-title":"Human Hepatic HepaRG Cells Maintain an Organotypic Phenotype with High Intrinsic CYP450 Activity\/Metabolism and Significantly Outperform Standard HepG2\/C3A Cells for Pharmaceutical and Therapeutic Applications","volume":"120","author":"Nelson","year":"2017","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1124\/dmd.123.001279_bib104","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/hep.24690","article-title":"Activation of autophagy protects against acetaminophen-induced hepatotoxicity","volume":"55","author":"Ni","year":"2012","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib105","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jhep.2016.04.025","article-title":"Removal of acetaminophen protein adducts by autophagy protects against acetaminophen-induced liver injury in mice","volume":"65","author":"Ni","year":"2016","journal-title":"J Hepatol"},{"key":"10.1124\/dmd.123.001279_bib106","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.toxlet.2020.12.005","article-title":"Mitochondrial protein adduct and superoxide generation are prerequisites for early activation of c-jun N-terminal kinase within the cytosol after an acetaminophen overdose in mice","volume":"338","author":"Nguyen","year":"2021","journal-title":"Toxicol Lett"},{"key":"10.1124\/dmd.123.001279_bib107","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1159\/000517231","article-title":"Use of CRRT and Plasmapheresis to Treat Simultaneous Iron and Acetaminophen Overdose","volume":"51","author":"Nye","year":"2022","journal-title":"Blood Purif"},{"key":"10.1124\/dmd.123.001279_bib108","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bbrc.2005.10.185","article-title":"Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity","volume":"339","author":"Okawa","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1124\/dmd.123.001279_bib109","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/S0140-6736(76)90030-1","article-title":"Reversal of experimental paracetamol toxicosis with N-acetylcysteine","volume":"2","author":"Piperno","year":"1976","journal-title":"Lancet"},{"key":"10.1124\/dmd.123.001279_bib110","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0022-3565(25)29665-3","article-title":"Acetaminophen-induced hepatic necrosis. 3. Cytochrome P-450-mediated covalent binding in vitro","volume":"187","author":"Potter","year":"1973","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/dmd.123.001279_bib111","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/S0140-6736(77)90612-2","article-title":"Treatment of paracetamol (acetaminophen) poisoning with N-acetylcysteine","volume":"2","author":"Prescott","year":"1977","journal-title":"Lancet"},{"key":"10.1124\/dmd.123.001279_bib112","doi-asserted-by":"crossref","first-page":"100973","DOI":"10.1016\/j.mam.2021.100973","article-title":"Autophagy in liver diseases: A review","volume":"82","author":"Qian","year":"2021","journal-title":"Mol Aspects Med"},{"key":"10.1124\/dmd.123.001279_bib113","doi-asserted-by":"crossref","first-page":"17940","DOI":"10.1074\/jbc.273.28.17940","article-title":"Identification of the hepatic protein targets of reactive metabolites of acetaminophen in vivo in mice using two-dimensional gel electrophoresis and mass spectrometry","volume":"273","author":"Qiu","year":"1998","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.123.001279_bib114","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.1073\/pnas.1804932115","article-title":"Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine","volume":"115","author":"Radi","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/dmd.123.001279_bib115","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/bs.apha.2019.01.007","article-title":"Acetaminophen hepatotoxicity: A mitochondrial perspective","volume":"85","author":"Ramachandran","year":"2019","journal-title":"Adv Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib116","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1089\/ars.2021.0102","article-title":"Oxidant Stress and Acetaminophen Hepatotoxicity: Mechanism-Based Drug Development","volume":"35","author":"Ramachandran","year":"2021","journal-title":"Antioxid Redox Signal"},{"key":"10.1124\/dmd.123.001279_bib117","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3390\/livers3020014","article-title":"Mitochondria in Acetaminophen-Induced Liver Injury and Recovery: A Concise Review","volume":"3","author":"Ramachandran","year":"2023","journal-title":"Livers"},{"key":"10.1124\/dmd.123.001279_bib118","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.taap.2011.01.004","article-title":"The impact of partial manganese superoxide dismutase (SOD2)-deficiency on mitochondrial oxidant stress, DNA fragmentation and liver injury during acetaminophen hepatotoxicity","volume":"251","author":"Ramachandran","year":"2011","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib119","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0003-9861(89)90504-3","article-title":"In vitro effects of acetaminophen metabolites and analogs on the respiration of mouse liver mitochondria","volume":"273","author":"Ramsay","year":"1989","journal-title":"Arch Biochem Biophys"},{"key":"10.1124\/dmd.123.001279_bib120","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1080\/15563650.2019.1676899","article-title":"Analysis of fomepizole safety based on a 16-year post-marketing experience in France","volume":"58","author":"Rasamison","year":"2020","journal-title":"Clin Toxicol (Phila)"},{"key":"10.1124\/dmd.123.001279_bib121","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/0041-008X(90)90254-R","article-title":"Early loss of large genomic DNA in vivo with accumulation of Ca2+ in the nucleus during acetaminophen-induced liver injury","volume":"106","author":"Ray","year":"1990","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib122","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cgh.2016.09.007","article-title":"An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure","volume":"15","author":"Roberts","year":"2017","journal-title":"Clin Gastroenterol Hepatol"},{"key":"10.1124\/dmd.123.001279_bib123","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3109\/15563650.2012.659252","article-title":"Acetaminophen and acetylcysteine dose and duration: past, present and future","volume":"50","author":"Rumack","year":"2012","journal-title":"Clin Toxicol (Phila)"},{"issue":"5 Pt 2, Suppl","key":"10.1124\/dmd.123.001279_bib124","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1542\/peds.62.5S.898","article-title":"Acetaminophen overdose: incidence, diagnosis, and management in 416 patients","volume":"62","author":"Rumack","year":"1978","journal-title":"Pediatrics"},{"key":"10.1124\/dmd.123.001279_bib125","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1001\/archinte.1981.00340030112020","article-title":"Acetaminophen overdose. 662 cases with evaluation of oral acetylcysteine treatment","volume":"141","author":"Rumack","year":"1981","journal-title":"Arch Intern Med"},{"key":"10.1124\/dmd.123.001279_bib126","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1021\/tx2003992","article-title":"Endogenous interleukin-4 regulates glutathione synthesis following acetaminophen-induced liver injury in mice","volume":"25","author":"Ryan","year":"2012","journal-title":"Chem Res Toxicol"},{"key":"10.1124\/dmd.123.001279_bib127","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.taap.2010.04.015","article-title":"c-Jun N-terminal kinase modulates oxidant stress and peroxynitrite formation independent of inducible nitric oxide synthase in acetaminophen hepatotoxicity","volume":"246","author":"Saito","year":"2010","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib128","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1002\/hep.23267","article-title":"Novel mechanisms of protection against acetaminophen hepatotoxicity in mice by glutathione and N-acetylcysteine","volume":"51","author":"Saito","year":"2010","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib129","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3109\/00365529509093237","article-title":"Protection against acetaminophen-induced liver injury in vivo by an iron chelator, deferoxamine","volume":"30","author":"Sakaida","year":"1995","journal-title":"Scand J Gastroenterol"},{"key":"10.1124\/dmd.123.001279_bib130","first-page":"479","article-title":"Endothelially derived nitric oxide affects the severity of early acetaminophen-induced hepatic injury in mice","volume":"13","author":"Salhanick","year":"2006","journal-title":"Acad Emerg Med"},{"key":"10.1124\/dmd.123.001279_bib131","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1124\/mol.112.079863","article-title":"Critical role for mixed-lineage kinase 3 in acetaminophen-induced hepatotoxicity","volume":"82","author":"Sharma","year":"2012","journal-title":"Mol Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib132","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/0041-008X(91)90028-D","article-title":"Acetaminophen-induced cytotoxicity in cultured mouse hepatocytes: correlation of nuclear Ca2+ accumulation and early DNA fragmentation with cell death","volume":"111","author":"Shen","year":"1991","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib133","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1742-7843.2004.pto950508.x","article-title":"Standard of care may not protect against acetaminophen-induced nephrotoxicity","volume":"95","author":"Slitt","year":"2004","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1124\/dmd.123.001279_bib134","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1056\/NEJM198812153192401","article-title":"Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985)","volume":"319","author":"Smilkstein","year":"1988","journal-title":"N Engl J Med"},{"key":"10.1124\/dmd.123.001279_bib135","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/0009-2797(89)90047-1","article-title":"Effect of acetaminophen on hepatic content and biliary efflux of glutathione disulfide in mice","volume":"70","author":"Smith","year":"1989","journal-title":"Chem Biol Interact"},{"key":"10.1124\/dmd.123.001279_bib136","doi-asserted-by":"crossref","first-page":"9814","DOI":"10.1016\/S0021-9258(18)81731-8","article-title":"Subcellular binding and effects on calcium homeostasis produced by acetaminophen and a nonhepatotoxic regioisomer, 3\u2032-hydroxyacetanilide, in mouse liver","volume":"264","author":"Tirmenstein","year":"1989","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.123.001279_bib137","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1016\/S0021-9258(19)39733-9","article-title":"Acetaminophen-induced oxidation of protein thiols. Contribution of impaired thiol-metabolizing enzymes and the breakdown of adenine nucleotides","volume":"265","author":"Tirmenstein","year":"1990","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.123.001279_bib138","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/toxsci\/kfaa188","article-title":"Mitochondrial Membrane Potential Drives Early Change in Mitochondrial Morphology After Acetaminophen Exposure","volume":"180","author":"Umbaugh","year":"2021","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib139","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1093\/toxsci\/kfab052","article-title":"Spatial Reconstruction of the Early Hepatic Transcriptomic Landscape After an Acetaminophen Overdose Using Single-Cell RNA-Sequencing","volume":"182","author":"Umbaugh","year":"2021","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib140","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/toxsci\/kfz222","article-title":"Identification of Serum Biomarkers to Distinguish Hazardous and Benign Aminotransferase Elevations","volume":"173","author":"Vazquez","year":"2020","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib141","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/toxsci\/kfac015","article-title":"Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways","volume":"187","author":"Vazquez","year":"2022","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib142","doi-asserted-by":"crossref","first-page":"101148","DOI":"10.1016\/j.redox.2019.101148","article-title":"Double deletion of PINK1 and Parkin impairs hepatic mitophagy and exacerbates acetaminophen-induced liver injury in mice","volume":"22","author":"Wang","year":"2019","journal-title":"Redox Biol"},{"key":"10.1124\/dmd.123.001279_bib143","doi-asserted-by":"crossref","first-page":"12169","DOI":"10.1073\/pnas.1412608111","article-title":"Circulating microRNA profiles in human patients with acetaminophen hepatotoxicity or ischemic hepatitis","volume":"111","author":"Ward","year":"2014","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/dmd.123.001279_bib144","doi-asserted-by":"crossref","first-page":"G355","DOI":"10.1152\/ajpgi.00303.2013","article-title":"Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury","volume":"307","author":"Weerasinghe","year":"2014","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1124\/dmd.123.001279_bib145","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.1016\/0006-2952(81)90576-1","article-title":"Drug-induced lipid peroxidation in mice--I. Modulation by monooxygenase activity, glutathione and selenium status","volume":"30","author":"Wendel","year":"1981","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib146","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1016\/0006-2952(79)90223-5","article-title":"Acute paracetamol intoxication of starved mice leads to lipid peroxidation in vivo","volume":"28","author":"Wendel","year":"1979","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib147","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1016\/0006-2952(82)90582-2","article-title":"Drug-induced lipid peroxidation in mice--II. Protection against paracetamol-induced liver necrosis by intravenous liposomally entrapped glutathione","volume":"31","author":"Wendel","year":"1982","journal-title":"Biochem Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib148","doi-asserted-by":"crossref","first-page":"35071","DOI":"10.1074\/jbc.M111.276089","article-title":"c-Jun N-terminal kinase (JNK)-dependent acute liver injury from acetaminophen or tumor necrosis factor (TNF) requires mitochondrial Sab protein expression in mice","volume":"286","author":"Win","year":"2011","journal-title":"J Biol Chem"},{"key":"10.1124\/dmd.123.001279_bib149","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1089\/ars.2022.0119","article-title":"c-Jun-N Terminal Kinase-Mediated Degradation of \u03b3-Glutamylcysteine Ligase Catalytic Subunit Inhibits GSH Recovery After Acetaminophen Treatment: Role in Sustaining JNK Activation and Liver Injury","volume":"38","author":"Win","year":"2023","journal-title":"Antioxid Redox Signal"},{"key":"10.1124\/dmd.123.001279_bib150","doi-asserted-by":"crossref","first-page":"1987","DOI":"10.1002\/hep.28486","article-title":"c-Jun N-terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5)-dependent pathway leading to inactivation of intramitochondrial Src","volume":"63","author":"Win","year":"2016","journal-title":"Hepatology"},{"key":"10.1124\/dmd.123.001279_bib151","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.jhep.2016.11.017","article-title":"Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure","volume":"66","author":"Woolbright","year":"2017","journal-title":"J Hepatol"},{"key":"10.1124\/dmd.123.001279_bib152","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/j.1742-7843.2012.00931.x","article-title":"Lysosomal instability and cathepsin B release during acetaminophen hepatotoxicity","volume":"111","author":"Woolbright","year":"2012","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"10.1124\/dmd.123.001279_bib153","doi-asserted-by":"crossref","first-page":"921","DOI":"10.3109\/00498254.2015.1026426","article-title":"Time course of acetaminophen-protein adducts and acetaminophen metabolites in circulation of overdose patients and in HepaRG cells","volume":"45","author":"Xie","year":"2015","journal-title":"Xenobiotica"},{"key":"10.1124\/dmd.123.001279_bib154","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.taap.2014.05.010","article-title":"Mechanisms of acetaminophen-induced cell death in primary human hepatocytes","volume":"279","author":"Xie","year":"2014","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib155","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.taap.2015.09.022","article-title":"Mitochondrial protein adducts formation and mitochondrial dysfunction during N-acetyl-m-aminophenol (AMAP)-induced hepatotoxicity in primary human hepatocytes","volume":"289","author":"Xie","year":"2015","journal-title":"Toxicol Appl Pharmacol"},{"key":"10.1124\/dmd.123.001279_bib156","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41419-020-2334-2","article-title":"Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates acetaminophen-induced acute liver failure","volume":"11","author":"Yamada","year":"2020","journal-title":"Cell Death Dis"},{"key":"10.1124\/dmd.123.001279_bib157","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/toxsci\/kfq208","article-title":"The oxygen tension modulates acetaminophen-induced mitochondrial oxidant stress and cell injury in cultured hepatocytes","volume":"117","author":"Yan","year":"2010","journal-title":"Toxicol Sci"},{"key":"10.1124\/dmd.123.001279_bib158","doi-asserted-by":"crossref","first-page":"459","DOI":"10.3109\/15563650.2016.1144889","article-title":"Potential adjunct treatment for high-risk acetaminophen overdose","volume":"54","author":"Yip","year":"2016","journal-title":"Clin Toxicol (Phila)"},{"key":"10.1124\/dmd.123.001279_bib159","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1097\/MJT.0b013e3181ff7ac0","article-title":"A gargantuan acetaminophen level in an acidemic patient treated solely with intravenous N-acetylcysteine","volume":"20","author":"Zell-Kanter","year":"2013","journal-title":"Am J Ther"},{"key":"10.1124\/dmd.123.001279_bib160","doi-asserted-by":"crossref","first-page":"e2903","DOI":"10.1038\/cddis.2017.295","article-title":"The role of MAP2 kinases and p38 kinase in acute murine liver injury models","volume":"8","author":"Zhang","year":"2017","journal-title":"Cell Death Dis"},{"key":"10.1124\/dmd.123.001279_bib161","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1080\/15548627.2019.1634944","article-title":"Topology-dependent, bifurcated mitochondrial quality control under starvation","volume":"16","author":"Zhou","year":"2020","journal-title":"Autophagy"}],"container-title":["Drug Metabolism and Disposition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624006603?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0090955624006603?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/dmd.123.001279","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T23:49:22Z","timestamp":1743637762000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0090955624006603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8]]},"references-count":161,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["S0090955624006603"],"URL":"https:\/\/doi.org\/10.1124\/dmd.123.001279","relation":{},"ISSN":["0090-9556"],"issn-type":[{"value":"0090-9556","type":"print"}],"subject":[],"published":{"date-parts":[[2024,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Central Mechanisms of Acetaminophen Hepatotoxicity: Mitochondrial Dysfunction by Protein Adducts and Oxidant Stress","name":"articletitle","label":"Article Title"},{"value":"Drug Metabolism and Disposition","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/dmd.123.001279","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}