{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T06:37:30Z","timestamp":1774420650147,"version":"3.50.1"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacological Research"],"published-print":{"date-parts":[[2025,1]]},"DOI":"10.1016\/j.phrs.2024.107540","type":"journal-article","created":{"date-parts":[[2024,12,8]],"date-time":"2024-12-08T00:07:00Z","timestamp":1733616420000},"page":"107540","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Paracetamol metabolism by endothelial cells \u2013 Potential mechanism underlying intravenous paracetamol-induced hypotension"],"prefix":"10.1016","volume":"211","author":[{"given":"Johs","family":"Dannesboe","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joakim A.","family":"Bastrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathrine Holm","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pelle","family":"Munck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten B.","family":"Thomsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clare L.","family":"Hawkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A.","family":"Jepps","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"4","key":"10.1016\/j.phrs.2024.107540_bib1","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.aucc.2010.06.004","article-title":"Paracetamol induced skin blood flow and blood pressure changes in febrile intensive care patients: an observational study","volume":"23","author":"Boyle","year":"2010","journal-title":"Aust. Crit. Care"},{"issue":"7","key":"10.1016\/j.phrs.2024.107540_bib2","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s00228-010-0806-5","article-title":"Paracetamol for intravenous use in medium--and intensive care patients: pharmacokinetics and tolerance","volume":"66","author":"de Maat","year":"2010","journal-title":"Eur. J. Clin. Pharm."},{"issue":"3","key":"10.1016\/j.phrs.2024.107540_bib3","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.aucc.2012.02.002","article-title":"Mechanism of paracetamol-induced hypotension in critically ill patients: a prospective observational cross-over study","volume":"26","author":"Kraj\u010dov\u00e1","year":"2013","journal-title":"Aust. Crit. Care"},{"issue":"10","key":"10.1016\/j.phrs.2024.107540_bib4","first-page":"1033","article-title":"Intravenous acetaminophen-induced hypotension: a review of the current literature","volume":"53","author":"Maxwell","year":"2019","journal-title":"Ann. Pharm."},{"issue":"3","key":"10.1016\/j.phrs.2024.107540_bib5","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1002\/nop2.943","article-title":"A narrative review of paracetamol-induced hypotension: keeping the patient safe","volume":"9","author":"Young","year":"2022","journal-title":"Nurs. Open"},{"issue":"9","key":"10.1016\/j.phrs.2024.107540_bib6","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1007\/s001340000614","article-title":"Effects of acetaminophen administration to patients in intensive care","volume":"26","author":"Mackenzie","year":"2000","journal-title":"Intensive Care Med."},{"issue":"4","key":"10.1016\/j.phrs.2024.107540_bib7","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1097\/j.pain.0000000000001474","article-title":"The paracetamol metabolite N-acetylp-benzoquinone imine reduces excitability in first- and second-order neurons of the pain pathway through actions on KV7 channels","volume":"160","author":"Ray","year":"2019","journal-title":"Pain"},{"issue":"1","key":"10.1016\/j.phrs.2024.107540_bib8","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24010650","article-title":"Analgesic action of acetaminophen via Kv7 channels","volume":"24","author":"Stampf","year":"2022","journal-title":"Int J. Mol. Sci."},{"key":"10.1016\/j.phrs.2024.107540_bib9","article-title":"Paracetamol - an old drug with new mechanisms of action","author":"Przyby\u0142a","year":"2020","journal-title":"Clin. Exp. Pharm. Physiol."},{"key":"10.1016\/j.phrs.2024.107540_bib10","doi-asserted-by":"crossref","DOI":"10.1111\/bph.16380","article-title":"A triple cysteine motif as major determinant of the modulation of neuronal K(V)7 channels by the paracetamol metabolite N-acetyl-p-benzo quinone imine","author":"Ray","year":"2024","journal-title":"Br. J. Pharmacol."},{"issue":"5","key":"10.1016\/j.phrs.2024.107540_bib11","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1161\/ATVBAHA.120.313997","article-title":"Acetaminophen (Paracetamol) metabolites induce vasodilation and hypotension by activating Kv7 potassium channels directly and indirectly","volume":"40","author":"van der Horst","year":"2020","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.phrs.2024.107540_bib12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3389\/fphys.2020.00727","article-title":"Cyclic AMP-dependent regulation of Kv7 voltage-gated potassium channels","volume":"11","author":"van der Horst","year":"2020","journal-title":"Front Physiol."},{"issue":"1","key":"10.1016\/j.phrs.2024.107540_bib13","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/s12974-017-1014-3","article-title":"AM404, paracetamol metabolite, prevents prostaglandin synthesis in activated microglia by inhibiting COX activity","volume":"14","author":"Saliba","year":"2017","journal-title":"J. Neuroinflamm."},{"issue":"4","key":"10.1016\/j.phrs.2024.107540_bib14","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":"10.1016\/j.phrs.2024.107540_bib15","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.freeradbiomed.2019.11.004","article-title":"Circulating myeloperoxidase is elevated in septic shock and is associated with systemic organ failure and mortality in critically ill patients","volume":"152","author":"Carr","year":"2020","journal-title":"Free Radic. Biol. Med"},{"issue":"1","key":"10.1016\/j.phrs.2024.107540_bib16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s40635-017-0157-y","article-title":"Myeloperoxidase can differentiate between sepsis and non-infectious SIRS and predicts mortality in intensive care patients with SIRS","volume":"5","author":"Schrijver","year":"2017","journal-title":"Intensive Care Med. Exp."},{"issue":"8","key":"10.1016\/j.phrs.2024.107540_bib17","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1016\/j.bcp.2009.11.024","article-title":"Acetaminophen (paracetamol) inhibits myeloperoxidase-catalyzed oxidant production and biological damage at therapeutically achievable concentrations","volume":"79","author":"Koelsch","year":"2010","journal-title":"Biochem Pharm."},{"issue":"3","key":"10.1016\/j.phrs.2024.107540_bib18","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/s10787-013-0172-x","article-title":"The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings","volume":"21","author":"Graham","year":"2013","journal-title":"Inflammopharmacology"},{"issue":"8","key":"10.1016\/j.phrs.2024.107540_bib19","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.freeradbiomed.2009.01.007","article-title":"Quantification of protein modification by oxidants","volume":"46","author":"Hawkins","year":"2009","journal-title":"Free Radic. Biol. Med."},{"issue":"1","key":"10.1016\/j.phrs.2024.107540_bib20","doi-asserted-by":"crossref","DOI":"10.1080\/19336950.2023.2217637","article-title":"Cycling matters: sex hormone regulation of vascular potassium channels","volume":"17","author":"Baldwin","year":"2023","journal-title":"Channels"},{"issue":"5","key":"10.1016\/j.phrs.2024.107540_bib21","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1074\/mcp.TIR118.001270","article-title":"Protein aggregation capture on microparticles enables multipurpose proteomics sample preparation","volume":"18","author":"Batth","year":"2019","journal-title":"Mol. Cell Proteom."},{"issue":"10","key":"10.1016\/j.phrs.2024.107540_bib22","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.105221","article-title":"Proteomic mapping reveals dysregulated angiogenesis in the cerebral arteries of rats with early-onset hypertension","volume":"299","author":"Bastrup","year":"2023","journal-title":"J. Biol. Chem."},{"issue":"1","key":"10.1016\/j.phrs.2024.107540_bib23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/s41592-019-0638-x","article-title":"DIA-NN: neural networks and interference correction enable deep proteome coverage in high throughput","volume":"17","author":"Demichev","year":"2020","journal-title":"Nat. Methods"},{"issue":"1-2","key":"10.1016\/j.phrs.2024.107540_bib24","doi-asserted-by":"crossref","DOI":"10.1002\/prca.201600123","article-title":"Proteomic analysis of acetaminophen-induced hepatotoxicity and identification of heme oxygenase 1 as a potential plasma biomarker of liver injury","volume":"11","author":"Gao","year":"2017","journal-title":"Proteom. Clin. Appl."},{"issue":"WebServer","key":"10.1016\/j.phrs.2024.107540_bib25","doi-asserted-by":"crossref","first-page":"W305","DOI":"10.1093\/nar\/gkp427","article-title":"ToppGene suite for gene list enrichment analysis and candidate gene prioritization","volume":"37","author":"Chen","year":"2009","journal-title":"Nucleic Acids Res."},{"issue":"3","key":"10.1016\/j.phrs.2024.107540_bib26","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/0009-2797(84)90145-5","article-title":"The covalent binding of acetaminophen to protein. Evidence for cysteine residues as major sites of arylation in vitro","volume":"48","author":"Streeter","year":"1984","journal-title":"Chem. -Biol. Interact."},{"issue":"5","key":"10.1016\/j.phrs.2024.107540_bib27","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1074\/mcp.M114.044305","article-title":"Extending the limits of quantitative proteome profiling with data-independent acquisition and application to acetaminophen-treated three-dimensional liver microtissues","volume":"14","author":"Bruderer","year":"2015","journal-title":"Mol. Cell Proteom."},{"key":"10.1016\/j.phrs.2024.107540_bib28","doi-asserted-by":"crossref","DOI":"10.1002\/ansa.202000182","article-title":"Determining site occupancy of acetaminophen covalent binding to target proteins in vitro","volume":"2","author":"Geib","year":"2021","journal-title":"Anal. Sci. Adv."},{"key":"10.1016\/j.phrs.2024.107540_bib29","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/978-3-642-00663-0_12","article-title":"Mechanisms of acetaminophen-induced liver necrosis","volume":"196","author":"Hinson","year":"2010","journal-title":"Handb. Exp. Pharm."},{"issue":"9","key":"10.1016\/j.phrs.2024.107540_bib30","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1161\/hh2101.099268","article-title":"Cytochrome p450 and vascular homeostasis","volume":"89","author":"Fleming","year":"2001","journal-title":"Circ. Res"},{"issue":"3","key":"10.1016\/j.phrs.2024.107540_bib31","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1515\/hsz-2019-0307","article-title":"Identification of new probe substrates for human CYP20A1","volume":"401","author":"Durairaj","year":"2020","journal-title":"Biol. Chem."},{"issue":"13","key":"10.1016\/j.phrs.2024.107540_bib32","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1089\/ars.2020.8030","article-title":"The Role of Myeloperoxidase in Biomolecule Modification, Chronic Inflammation, and Disease","volume":"32","author":"Davies","year":"2020","journal-title":"Antioxid. Redox Signal"},{"issue":"2","key":"10.1016\/j.phrs.2024.107540_bib33","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1177\/1753425920980078","article-title":"Early prolonged neutrophil activation in critically ill patients with sepsis","volume":"27","author":"T\u00f6rnblom","year":"2021","journal-title":"Innate Immun."},{"issue":"9","key":"10.1016\/j.phrs.2024.107540_bib34","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1161\/ATVBAHA.118.311360","article-title":"Investigating the role of G protein \u03b2\u03b3 in Kv7-dependent relaxations of the rat vasculature","volume":"38","author":"Stott","year":"2018","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"4","key":"10.1016\/j.phrs.2024.107540_bib35","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1161\/ATVBAHA.114.303405","article-title":"Contribution of kv7.4\/kv7.5 heteromers to intrinsic and calcitonin gene-related peptide-induced cerebral reactivity","volume":"34","author":"Chadha","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.phrs.2024.107540_bib36","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.mce.2006.12.022","article-title":"Hexose 6-phosphate dehydrogenase (H6PD) and corticosteroid metabolism","volume":"265-266","author":"White","year":"2007","journal-title":"Mol. Cell. Endocrinol."},{"issue":"6","key":"10.1016\/j.phrs.2024.107540_bib37","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.cmet.2018.04.003","article-title":"Aldolase B-mediated fructose metabolism drives metabolic reprogramming of colon cancer liver metastasis","volume":"27","author":"Bu","year":"2018","journal-title":"Cell Metab."},{"issue":"16","key":"10.1016\/j.phrs.2024.107540_bib38","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.14554","article-title":"Divergent effects of glutathione depletion on isocitrate dehydrogenase 1 and the pentose phosphate pathway in hamster liver","volume":"8","author":"Jin","year":"2020","journal-title":"Physiol. Rep."},{"key":"10.1016\/j.phrs.2024.107540_bib39","doi-asserted-by":"crossref","first-page":"21373","DOI":"10.1038\/srep21373","article-title":"Acetaminophen induces accumulation of functional rat CYP3A via polyubiquitination dysfunction","volume":"6","author":"Santoh","year":"2016","journal-title":"Sci. Rep."},{"issue":"13","key":"10.1016\/j.phrs.2024.107540_bib40","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/0006-2952(87)90132-8","article-title":"The mechanism of prevention of paracetamol-induced hepatotoxicity by 3,5-dialkyl substitution. The roles of glutathione depletion and oxidative stress","volume":"36","author":"van de Straat","year":"1987","journal-title":"Biochem Pharm."},{"issue":"9","key":"10.1016\/j.phrs.2024.107540_bib41","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1016\/S0006-2952(97)00048-8","article-title":"Sinusoidal endothelial cells as a target for acetaminophen toxicity. Direct action versus requirement for hepatocyte activation in different mouse strains","volume":"53","author":"DeLeve","year":"1997","journal-title":"Biochem. Pharmacol."},{"issue":"1","key":"10.1016\/j.phrs.2024.107540_bib42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13318-011-0024-2","article-title":"Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity","volume":"36","author":"Khojasteh","year":"2011","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"10.1016\/j.phrs.2024.107540_bib43","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.freeradbiomed.2016.11.019","article-title":"Cytochrome P450 enzymes but not NADPH oxidases are the source of the NADPH-dependent lucigenin chemiluminescence in membrane assays","volume":"102","author":"Rezende","year":"2017","journal-title":"Free Radic. Biol. Med"},{"issue":"12","key":"10.1016\/j.phrs.2024.107540_bib44","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/nbt1210-1248","article-title":"Towards a knowledge-based Human Protein Atlas","volume":"28","author":"Uhlen","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.phrs.2024.107540_bib45","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/ncomms1559","article-title":"TRPA1 mediates spinal antinociception induced by acetaminophen and the cannabinoid \u0394(9)-tetrahydrocannabiorcol","volume":"2","author":"Andersson","year":"2011","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.phrs.2024.107540_bib46","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-13054-3","article-title":"Reactive metabolites of acetaminophen activate and sensitize the capsaicin receptor TRPV1","volume":"7","author":"Eberhardt","year":"2017","journal-title":"Sci. Rep."},{"issue":"9","key":"10.1016\/j.phrs.2024.107540_bib47","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0012748","article-title":"TRPV1 in brain is involved in acetaminophen-induced antinociception","volume":"5","author":"Mallet","year":"2010","journal-title":"PLoS One"}],"container-title":["Pharmacological Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661824004857?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1043661824004857?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T13:47:16Z","timestamp":1736430436000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1043661824004857"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1]]},"references-count":47,"alternative-id":["S1043661824004857"],"URL":"https:\/\/doi.org\/10.1016\/j.phrs.2024.107540","relation":{},"ISSN":["1043-6618"],"issn-type":[{"value":"1043-6618","type":"print"}],"subject":[],"published":{"date-parts":[[2025,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Paracetamol metabolism by endothelial cells \u2013 Potential mechanism underlying intravenous paracetamol-induced hypotension","name":"articletitle","label":"Article Title"},{"value":"Pharmacological Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phrs.2024.107540","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 The Authors. Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"107540"}}