{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:16:39Z","timestamp":1778940999086,"version":"3.51.4"},"reference-count":108,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FEDER funds via COMPETE, Portugal 2020\u2014Operational Programme for Competitiveness and Internationalization (POCI)","award":["POCI-01-0145-FEDER-032188"],"award-info":[{"award-number":["POCI-01-0145-FEDER-032188"]}]},{"name":"FEDER funds via COMPETE, Portugal 2020\u2014Operational Programme for Competitiveness and Internationalization (POCI)","award":["PTDC\/MEC-CAR\/32188\/2017"],"award-info":[{"award-number":["PTDC\/MEC-CAR\/32188\/2017"]}]},{"name":"FEDER funds via COMPETE, Portugal 2020\u2014Operational Programme for Competitiveness and Internationalization (POCI)","award":["UI\/BD\/150816\/2020"],"award-info":[{"award-number":["UI\/BD\/150816\/2020"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["POCI-01-0145-FEDER-032188"],"award-info":[{"award-number":["POCI-01-0145-FEDER-032188"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["PTDC\/MEC-CAR\/32188\/2017"],"award-info":[{"award-number":["PTDC\/MEC-CAR\/32188\/2017"]}]},{"name":"Portuguese Foundation for Science and Technology (FCT)","award":["UI\/BD\/150816\/2020"],"award-info":[{"award-number":["UI\/BD\/150816\/2020"]}]},{"name":"FCT and MedInUP","award":["POCI-01-0145-FEDER-032188"],"award-info":[{"award-number":["POCI-01-0145-FEDER-032188"]}]},{"name":"FCT and MedInUP","award":["PTDC\/MEC-CAR\/32188\/2017"],"award-info":[{"award-number":["PTDC\/MEC-CAR\/32188\/2017"]}]},{"name":"FCT and MedInUP","award":["UI\/BD\/150816\/2020"],"award-info":[{"award-number":["UI\/BD\/150816\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Cysteinyl leukotrienes (CysLT) are potent vascular leakage-promoting agents but have been scarcely explored in human septic shock (SS). We evaluated CysLT at admission and during hospitalization and their correlation with endothelial dysfunction, inflammation, oxidative stress, the renin\u2013angiotensin\u2013aldosterone system, and cardiac, renal, respiratory, and hepatic parameters in SS patients. Blood and spot-urine samples were collected at days 1\u20132 (admission), 3\u20134, and 5\u20138 in SS patients (n = 13) and at a single time point in controls (n = 22). Urinary CysLT (u-CysLT) and isoprostanes, plasma, and urinary angiotensinogen, serum myeloperoxidase, and IL-10 were quantified by ELISA. Serum intercellular-adhesion molecule-1, vascular cell-adhesion molecule-1, E-selectin, tumor necrosis factor-\u03b1, IL-1\u03b2, and IL-6 were measured by multiplex immunoassays. Routine markers were evaluated using automated analyzers. At admission, SS patients had increased u-CysLT, endothelial activation, inflammation, oxidative stress, and plasma and urinary angiotensinogen, as well as cardiac, respiratory, hepatic, and renal injury\/dysfunction. There were no changes in u-CysLT during hospitalization. Both correlation and multivariate analyses showed positive relationships of u-CysLT with endothelial activation, inflammation, oxidative stress, proteinuria, and hepatic injury\/dysfunction markers. These results suggest that u-CysLT may be potential non-invasive biomarkers for monitoring the pathophysiological mechanisms underlying SS, as well as putative therapeutic targets.<\/jats:p>","DOI":"10.3390\/biomedicines10112845","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T11:46:43Z","timestamp":1667908003000},"page":"2845","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Urinary Cysteinyl Leukotrienes as Biomarkers of Endothelial Activation, Inflammation and Oxidative Stress and Their Relationship with Organ Dysfunction in Human Septic Shock"],"prefix":"10.3390","volume":"10","author":[{"given":"Marta","family":"Reina-Couto","sequence":"first","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa, Universidade do Porto (MedInUP), 4200-319 Porto, Portugal"},{"name":"Servi\u00e7o de Medicina Intensiva, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Servi\u00e7o de Farmacologia Cl\u00ednica, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Marisa","family":"Santos-Oliveira","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Patr\u00edcia","family":"Pereira-Terra","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa, Universidade do Porto (MedInUP), 4200-319 Porto, Portugal"}]},{"given":"Carolina","family":"Silva-Pereira","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa, Universidade do Porto (MedInUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8388-1848","authenticated-orcid":false,"given":"Janete","family":"Quelhas-Santos","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"\u00c1lvaro","family":"Duarte","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6813-314X","authenticated-orcid":false,"given":"Sandra","family":"Martins","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Patologia Cl\u00ednica, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"EPIUnit, Instituto de Sa\u00fade P\u00fablica, Universidade do Porto, 4050-600 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3663-7500","authenticated-orcid":false,"given":"Paula","family":"Serr\u00e3o","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa, Universidade do Porto (MedInUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9356-3272","authenticated-orcid":false,"given":"Cl\u00e1udia Camila","family":"Dias","sequence":"additional","affiliation":[{"name":"Departamento de Medicina da Comunidade, Informa\u00e7\u00e3o e Decis\u00e3o em Sa\u00fade, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o em Tecnologias e Servi\u00e7os de Sa\u00fade (CINTESI), Universidade do Porto, 4200-450 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9509-0613","authenticated-orcid":false,"given":"Manuela","family":"Morato","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Farmacologia, Departamento de Ci\u00eancias do Medicamento, Faculdade de Farm\u00e1cia da Universidade do Porto, 4050-313 Porto, Portugal"},{"name":"LAQV\/REQUIMTE, Faculdade de Farm\u00e1cia da Universidade do Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4836-6311","authenticated-orcid":false,"given":"Jo\u00e3o T.","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Patologia Cl\u00ednica, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"EPIUnit, Instituto de Sa\u00fade P\u00fablica, Universidade do Porto, 4050-600 Porto, Portugal"},{"name":"Departamento de Bioqu\u00edmica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Roberto","family":"Roncon-Albuquerque","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Medicina Intensiva, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Departamento de Cirurgia e Fisiologia, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Jos\u00e9-Artur","family":"Paiva","sequence":"additional","affiliation":[{"name":"Servi\u00e7o de Medicina Intensiva, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, 4200-319 Porto, Portugal"},{"name":"Departamento de Medicina, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Albino-Teixeira","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa, Universidade do Porto (MedInUP), 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7230-5020","authenticated-orcid":false,"given":"Teresa","family":"Sousa","sequence":"additional","affiliation":[{"name":"Departamento de Biomedicina\u2014Unidade de Farmacologia e Terap\u00eautica, Faculdade de Medicina da Universidade do Porto, 4200-319 Porto, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Farmacol\u00f3gica e Inova\u00e7\u00e3o Medicamentosa, Universidade do Porto (MedInUP), 4200-319 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1056\/NEJMra1208623","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4161\/viru.25436","article-title":"Host innate immune responses to sepsis","volume":"5","author":"Wiersinga","year":"2014","journal-title":"Virulence"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.immuni.2014.04.001","article-title":"Sepsis: Current dogma and new perspectives","volume":"40","author":"Deutschman","year":"2014","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41581-018-0005-7","article-title":"Mechanisms and treatment of organ failure in sepsis","volume":"14","author":"Lelubre","year":"2018","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1001\/jama.2016.0288","article-title":"Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Seymour","year":"2016","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ccc.2017.08.005","article-title":"Pathophysiology of Septic Shock","volume":"34","author":"Russell","year":"2018","journal-title":"Crit. Care Clin."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1001\/jama.2016.0289","article-title":"Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Phillips","year":"2016","journal-title":"JAMA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1186\/s13054-020-02993-5","article-title":"Biomarkers of sepsis: Time for a reappraisal","volume":"24","author":"Pierrakos","year":"2020","journal-title":"Crit. Care"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ccc.2019.08.003","article-title":"Procalcitonin: Where Are We Now?","volume":"36","author":"Hamade","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1007\/s00134-020-06151-x","article-title":"Incidence and mortality of hospital- and ICU-treated sepsis: Results from an updated and expanded systematic review and meta-analysis","volume":"46","author":"Mellhammar","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1001\/jama.2017.13836","article-title":"Incidence and Trends of Sepsis in US Hospitals Using Clinical vs. Claims Data, 2009\u20132014","volume":"318","author":"Rhee","year":"2017","journal-title":"JAMA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1056\/NEJMoa1401602","article-title":"A randomized trial of protocol-based care for early septic shock","volume":"370","author":"Pro","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1056\/NEJMoa1404380","article-title":"Goal-directed resuscitation for patients with early septic shock","volume":"371","author":"Investigators","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJMoa1500896","article-title":"Trial of early, goal-directed resuscitation for septic shock","volume":"372","author":"Mouncey","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S1473-3099(15)70112-X","article-title":"Sepsis: A roadmap for future research","volume":"15","author":"Cohen","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.mcna.2020.02.011","article-title":"Sepsis and Septic Shock-Basics of diagnosis, pathophysiology and clinical decision making","volume":"104","author":"Font","year":"2020","journal-title":"Med. Clin. North. Am."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2017.36","article-title":"The immunopathology of sepsis and potential therapeutic targets","volume":"17","author":"Scicluna","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1056\/NEJM198709103171101","article-title":"A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock","volume":"317","author":"Bone","year":"1987","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jama.1995.03520360048038","article-title":"Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group","volume":"273","author":"Abraham","year":"1995","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/00003246-199401000-00008","article-title":"Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: A randomized, open-label, placebo-controlled multicenter trial","volume":"22","author":"Fisher","year":"1994","journal-title":"Crit. Care Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1056\/NEJM199703273361303","article-title":"The effects of ibuprofen on the physiology and survival of patients with sepsis. The Ibuprofen in Sepsis Study Group","volume":"336","author":"Bernard","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nedeva, C. (2021). Inflammation and Cell Death of the Innate and Adaptive Immune System during Sepsis. Biomolecules, 11.","DOI":"10.3390\/biom11071011"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/cvr\/cvaa070","article-title":"The effects of sepsis on endothelium and clinical implications","volume":"117","author":"Dolmatova","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1164\/rccm.201910-1911TR","article-title":"Endothelial Responses in Sepsis","volume":"202","author":"Joffre","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0749-0704(18)30439-1","article-title":"Proposed role for leukotrienes in the pathophysiology of multiple systems organ failure","volume":"5","author":"Sprague","year":"1989","journal-title":"Crit. Care Clin."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1126\/science.4048937","article-title":"Leukotrienes as mediators in tissue trauma","volume":"230","author":"Denzlinger","year":"1985","journal-title":"Science"},{"key":"ref_29","first-page":"3","article-title":"Significance of lipid mediators in shock states","volume":"27","author":"Lefer","year":"1989","journal-title":"Circ. Shock"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1096\/fasebj.9.11.7649404","article-title":"Specificity of expression and effects of eicosanoid mediators in normal physiology and human diseases","volume":"9","author":"Goetzl","year":"1995","journal-title":"FASEB J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1172\/JCI111312","article-title":"The biologically active leukotrienes. Biosynthesis, metabolism, receptors, functions, and pharmacology","volume":"73","author":"Lewis","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/0092-8674(91)90556-E","article-title":"A novel arachidonic acid-selective cytosolic PLA2 contains a Ca2+-dependent translocation domain with homology to PKC and GAP","volume":"65","author":"Clark","year":"1991","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"19818","DOI":"10.1016\/S0021-9258(17)45446-9","article-title":"Correlation between expression of 5-lipoxygenase-activating protein, 5-lipoxygenase, and cellular leukotriene synthesis","volume":"265","author":"Reid","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0304-4165(85)90160-6","article-title":"Purification and characterisation of leukotriene A4 hydrolase from rat neutrophils","volume":"840","author":"Evans","year":"1985","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1073\/pnas.90.5.2015","article-title":"Purification to homogeneity and the N-terminal sequence of human leukotriene C4 synthase: A homodimeric glutathione S-transferase composed of 18-kDa subunits","volume":"90","author":"Nicholson","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1073\/pnas.79.4.1088","article-title":"Interconversion of leukotrienes catalyzed by purified gamma-glutamyl transpeptidase: Concomitant formation of leukotriene D4 and gamma-glutamyl amino acids","volume":"79","author":"Anderson","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","first-page":"27","article-title":"Conversion of leukotriene D4 to leukotriene E4 by a dipeptidase released from the specific granule of human polymorphonuclear leucocytes","volume":"48","author":"Lee","year":"1983","journal-title":"Immunology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/0006-291X(81)91562-X","article-title":"Rapid in vivo metabolism of leukotriene C3 in the monkey Macaca irus","volume":"101","author":"Orning","year":"1981","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1203\/00006450-199501000-00001","article-title":"Leukotrienes: Biosynthesis, Metabolism, and Pathophysiologic Significance","volume":"37","author":"Mayatepek","year":"1995","journal-title":"Pediatr. Res."},{"key":"ref_40","first-page":"H244","article-title":"Entry rate and metabolism of leukotriene C4 into vascular compartment in healthy subjects","volume":"263","author":"Maclouf","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2432958","DOI":"10.1155\/2017\/2432958","article-title":"Role of the Cysteinyl Leukotrienes in the Pathogenesis and Progression of Cardiovascular Diseases","volume":"2017","author":"Colazzo","year":"2017","journal-title":"Mediat. Inflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"20820","DOI":"10.1074\/jbc.M203163200","article-title":"Targeted gene disruption reveals the role of cysteinyl leukotriene 1 receptor in the enhanced vascular permeability of mice undergoing acute inflammatory responses","volume":"277","author":"Maekawa","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"288","DOI":"10.4168\/aair.2014.6.4.288","article-title":"Cysteinyl Leukotrienes and Their Receptors; Emerging Concepts","volume":"6","author":"Kanaoka","year":"2014","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"11685","DOI":"10.1073\/pnas.0905364106","article-title":"GPR17 is a negative regulator of the cysteinyl leukotriene 1 receptor response to leukotriene D4","volume":"106","author":"Maekawa","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10967","DOI":"10.1074\/jbc.C113.453704","article-title":"Identification of GPR99 protein as a potential third cysteinyl leukotriene receptor with a preference for leukotriene E4 ligand","volume":"288","author":"Kanaoka","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3655","DOI":"10.1097\/00003246-200011000-00020","article-title":"Cysteinyl-leukotriene generation as a biomarker for survival in the critically ill","volume":"28","author":"Morlion","year":"2000","journal-title":"Crit. Care Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22608","DOI":"10.1074\/jbc.M103562200","article-title":"Attenuated zymosan-induced peritoneal vascular permeability and IgE-dependent passive cutaneous anaphylaxis in mice lacking leukotriene C4 synthase","volume":"276","author":"Kanaoka","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46129","DOI":"10.1074\/jbc.M407057200","article-title":"Targeted gene disruption reveals the role of the cysteinyl leukotriene 2 receptor in increased vascular permeability and in bleomycin-induced pulmonary fibrosis in mice","volume":"279","author":"Beller","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3360","DOI":"10.1161\/01.CIR.0000147775.50954.AA","article-title":"Directed vascular expression of human cysteinyl leukotriene 2 receptor modulates endothelial permeability and systemic blood pressure","volume":"110","author":"Hui","year":"2004","journal-title":"Circulation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1084\/jem.20020044","article-title":"Cysteinyl Leukotrienes and Uridine Diphosphate Induce Cytokine Generation by Human Mast Cells Through an Interleukin 4\u2013regulated Pathway that Is Inhibited by Leukotriene Receptor Antagonists","volume":"195","author":"Mellor","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"S580","DOI":"10.1093\/clinids\/9.Supplement_5.S580","article-title":"Role of leukotrienes in endotoxin action in vivo","volume":"9","author":"Keppler","year":"1987","journal-title":"Rev. Infect. Dis"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.4049\/jimmunol.174.3.1616","article-title":"Opposing and hierarchical roles of leukotrienes in local innate immune versus vascular responses in a model of sepsis","volume":"174","author":"Benjamim","year":"2005","journal-title":"J. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1139\/cjpp-2014-0191","article-title":"Montelukast reduces sepsis-induced lung and renal injury in rats","volume":"92","author":"Khodir","year":"2014","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.pathophys.2011.02.003","article-title":"Montelukast, a leukotriene receptor antagonist abrogates lipopolysaccharide-induced toxicity and oxidative stress in rat liver","volume":"18","author":"Mohamadin","year":"2011","journal-title":"Pathophysiology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1100\/tsw.2011.122","article-title":"The effects of montelukast on antioxidant enzymes and proinflammatory cytokines on the heart, liver, lungs, and kidneys in a rat model of cecal ligation and puncture-induced sepsis","volume":"11","author":"Coskun","year":"2011","journal-title":"Sci. World J."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1365-2362.2009.02234.x","article-title":"A catalogue of reporting guidelines for health research","volume":"40","author":"Simera","year":"2010","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"L746","DOI":"10.1152\/ajplung.00166.2014","article-title":"Cell-cell interactions and bronchoconstrictor eicosanoid reduction with inhaled carbon monoxide and resolvin D1","volume":"307","author":"Shinohara","year":"2014","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1097\/00024382-199704000-00007","article-title":"Pathophysiologic plasma levels of leukotriene C4 in relation to the hemodynamic dysfunction and mediator release of graded bacteremia","volume":"7","author":"Zeltsman","year":"1997","journal-title":"Shock"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/00024382-200006000-00010","article-title":"The cardiovascular hemodynamics and leukotriene kinetics during prostacyclin and anti-prostacyclin antibody infusions in septic shock","volume":"13","author":"Tran","year":"2000","journal-title":"Shock"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1054\/plef.1999.0023","article-title":"Ibuprofen attenuates cardiopulmonary dysfunction by modifying vascular tone in endotoxemia","volume":"60","author":"Heidemann","year":"1999","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1002\/hep.1840200406","article-title":"Cysteinyl leukotrienes in the urine of patients with liver diseases","volume":"20","author":"Uemura","year":"1994","journal-title":"Hepatology"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1042\/cs0800497","article-title":"Enhanced urinary excretion of leukotriene E4 by patients with multiple trauma with or without adult respiratory distress syndrome","volume":"80","author":"Fauler","year":"1991","journal-title":"Clin. Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1089\/ars.2021.0027","article-title":"Oxidative stress and endothelial dysfunction in sepsis and acute inflammation","volume":"35","author":"Joffre","year":"2021","journal-title":"Antioxid Redox Signal."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.cyto.2016.08.028","article-title":"Endothelial adhesion molecules and multiple organ failure in patients with severe sepsis","volume":"88","author":"Amalakuhan","year":"2016","journal-title":"Cytokine"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1164\/ajrccm.156.2.9509017","article-title":"Soluble E-selectin levels in sepsis and critical illness. Correlation with infection and hemodynamic dysfunction","volume":"156","author":"Cummings","year":"1997","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1038\/srep03274","article-title":"Cysteinyl leukotrienes regulate endothelial cell inflammatory and proliferative signals through CysLT2 and CysLT1 receptors","volume":"3","author":"Duah","year":"2013","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.4049\/jimmunol.162.8.4943","article-title":"A fatal cytokine-induced systemic inflammatory response reveals a critical role for NK cells","volume":"162","author":"Carson","year":"1999","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"321s","DOI":"10.1378\/chest.112.6_Supplement.321S","article-title":"Proinflammatory and anti-inflammatory cytokines as mediators in the pathogenesis of septic shock","volume":"112","author":"Dinarello","year":"1997","journal-title":"Chest"},{"key":"ref_70","first-page":"39","article-title":"Modulation of IL-1 inflammatory and immunomodulatory properties by IL-6","volume":"2","author":"Hauptmann","year":"1991","journal-title":"Eur. Cytokine Netw."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1056\/NEJM199006073222302","article-title":"Activation of coagulation after administration of tumor necrosis factor to normal subjects","volume":"322","author":"Wortel","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1182\/blood.V86.4.1243.bloodjournal8641243","article-title":"Interleukin-6 family of cytokines and gp130","volume":"86","author":"Kishimoto","year":"1995","journal-title":"Blood"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1097\/00003246-200201001-00008","article-title":"Interleukin-10: A complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug","volume":"30","author":"Oberholzer","year":"2002","journal-title":"Crit. Care Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1006\/bbrc.2001.4865","article-title":"Neutrophils, endothelial cells, and cysteinyl leukotrienes: A new approach to neutrophil-dependent inflammation?","volume":"283","author":"Sala","year":"2001","journal-title":"Biochem. Biophys Res. Commun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3109\/10408363.2013.764490","article-title":"Biomarkers of sepsis","volume":"50","author":"Faix","year":"2013","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e13333","DOI":"10.1111\/eci.13333","article-title":"The role of resistin and myeloperoxidase in severe sepsis and septic shock: Results from the ALBIOS trial","volume":"50","author":"Bonaventura","year":"2020","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/bja\/aeg034","article-title":"Oxidative stress and gene expression in sepsis","volume":"90","author":"Macdonald","year":"2003","journal-title":"Br. J. Anaesth"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"H2563","DOI":"10.1152\/ajpheart.00435.2003","article-title":"Interaction of myeloperoxidase with vascular NAD(P)H oxidase-derived reactive oxygen species in vasculature: Implications for vascular diseases","volume":"285","author":"Zhang","year":"2003","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1097\/SHK.0b013e318217025a","article-title":"Plasma Biomarkers of Oxidant Stress and Development of Organ Failure in Severe Sepsis","volume":"36","author":"Ware","year":"2011","journal-title":"Shock"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.plefa.2005.07.008","article-title":"Amelioration of sepsis-induced hepatic and ileal injury in rats by the leukotriene receptor blocker montelukast","volume":"73","author":"Sener","year":"2005","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.4049\/jimmunol.173.3.1503","article-title":"Cysteinyl leukotrienes and their receptors: Cellular distribution and function in immune and inflammatory responses","volume":"173","author":"Kanaoka","year":"2004","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1097\/01.CCM.0000050454.01978.3B","article-title":"2001 SCCM\/ESICM\/ACCP\/ATS\/SIS International Sepsis Definitions Conference","volume":"31","author":"Levy","year":"2003","journal-title":"Crit. Care Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2215\/CJN.07310717","article-title":"Sepsis-Associated AKI","volume":"13","author":"Prowle","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1159\/000286037","article-title":"Urinary angiotensinogen accurately reflects intrarenal Renin-Angiotensin system activity","volume":"31","author":"Urushihara","year":"2010","journal-title":"Am. J. Nephrol."},{"key":"ref_85","first-page":"108","article-title":"Urinary Angiotensinogen as a Novel Biomarker of Intrarenal Renin-Angiotensin System in Chronic Kidney Disease","volume":"6","author":"Kobori","year":"2011","journal-title":"Int. Rev. Thromb."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"357","DOI":"10.2169\/internalmedicine.3624-19","article-title":"The Urinary Angiotensinogen to Urinary Albumin Ratio Reflects Whether the Renin-angiotensin System in the Kidney Is Activated due to Filtration of Plasma Angiotensinogen through the Damaged Glomeruli or the Production of Angiotensinogen in the Proximal Tubules","volume":"59","author":"Ohashi","year":"2020","journal-title":"Intern. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/ckj\/sfx087","article-title":"Angiotensinogen as a biomarker of acute kidney injury","volume":"10","author":"Sanchez","year":"2017","journal-title":"Clin. Kidney J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"R69","DOI":"10.1186\/cc12612","article-title":"Urinary angiotensinogen predicts adverse outcomes among acute kidney injury patients in the intensive care unit","volume":"17","author":"Alge","year":"2013","journal-title":"Crit. Care"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4103\/2321-3868.132689","article-title":"Advances in sepsis-associated liver dysfunction","volume":"2","author":"Wang","year":"2014","journal-title":"Burn. Trauma"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"R93","DOI":"10.1186\/cc7923","article-title":"Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction","volume":"13","author":"Hofer","year":"2009","journal-title":"Crit. Care"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/S0002-9610(97)89552-9","article-title":"Serial blood lactate levels can predict the development of multiple organ failure following septic shock","volume":"171","author":"Bakker","year":"1996","journal-title":"Am. J. Surg."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1097\/CCM.0b013e3181a0f919","article-title":"Association between blood lactate levels, Sequential Organ Failure Assessment subscores, and 28-day mortality during early and late intensive care unit stay: A retrospective observational study","volume":"37","author":"Jansen","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/2110-5820-3-12","article-title":"Clinical use of lactate monitoring in critically ill patients","volume":"3","author":"Bakker","year":"2013","journal-title":"Ann. Intensive Care"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1164\/rccm.200912-1918OC","article-title":"Early lactate-guided therapy in intensive care unit patients: A multicenter, open-label, randomized controlled trial","volume":"182","author":"Jansen","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/SHK.0000000000000861","article-title":"Mortality is Greater in Septic Patients With Hyperlactatemia Than With Refractory Hypotension","volume":"48","author":"Gotmaker","year":"2017","journal-title":"Shock"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.ccc.2019.08.009","article-title":"Lactate: Where Are We Now?","volume":"36","author":"Bakker","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1001\/jama.2019.0071","article-title":"Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs. Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial","volume":"321","author":"Hernandez","year":"2019","journal-title":"JAMA"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1007\/s00134-018-5213-x","article-title":"The ten pitfalls of lactate clearance in sepsis","volume":"45","author":"Hernandez","year":"2019","journal-title":"Intensive Care Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"663560","DOI":"10.3389\/fnut.2021.663560","article-title":"Role of the Heart in Lactate Shuttling","volume":"8","author":"Brooks","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"5591","DOI":"10.1113\/jphysiol.2009.178350","article-title":"Cell-cell and intracellular lactate shuttles","volume":"587","author":"Brooks","year":"2009","journal-title":"J. Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"538.e9","DOI":"10.1016\/j.jcrc.2012.11.022","article-title":"Severe abnormalities in microvascular perfused vessel density are associated to organ dysfunctions and mortality and can be predicted by hyperlactatemia and norepinephrine requirements in septic shock patients","volume":"28","author":"Hernandez","year":"2013","journal-title":"J. Crit. Care"},{"key":"ref_102","first-page":"2827","article-title":"Blood lactate monitoring in critically ill patients: A systematic health technology assessment","volume":"37","author":"Jansen","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/2110-5820-2-44","article-title":"Relationship of systemic, hepatosplanchnic, and microcirculatory perfusion parameters with 6-hour lactate clearance in hyperdynamic septic shock patients: An acute, clinical-physiological, pilot study","volume":"2","author":"Hernandez","year":"2012","journal-title":"Ann. Intensive Care"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.maturitas.2003.10.015","article-title":"Crosstalk between inflammation and thrombosis","volume":"47","author":"Esmon","year":"2004","journal-title":"Maturitas"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"88ps25","DOI":"10.1126\/scitranslmed.3002011","article-title":"Broken barriers: A new take on sepsis pathogenesis","volume":"3","author":"Goldenberg","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1097\/EJA.0b013e328324b7c2","article-title":"The impact of ischaemia-reperfusion on the blood vessel","volume":"26","author":"Gourdin","year":"2009","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/bja\/aer093","article-title":"Oxidative stress and mitochondrial dysfunction in sepsis","volume":"107","author":"Galley","year":"2011","journal-title":"Br. J. Anaesth."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1097\/CCM.0000000000002206","article-title":"Relationship Between Alternative Resuscitation Strategies, Host Response and Injury Biomarkers, and Outcome in Septic Shock: Analysis of the Protocol-Based Care for Early Septic Shock Study","volume":"45","author":"Kellum","year":"2017","journal-title":"Crit. Care Med."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/11\/2845\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:23Z","timestamp":1760145143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/10\/11\/2845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,8]]},"references-count":108,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["biomedicines10112845"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines10112845","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,8]]}}}