{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:20:49Z","timestamp":1792628449862,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T00:00:00Z","timestamp":1508284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sepsis is a severe and multifactorial disease with a high mortality rate. It represents a strong inflammatory response to an infection and is associated with vascular inflammation and oxidative\/nitrosative stress. Here, we studied the underlying time responses in the widely used lipopolysaccharide (LPS)-induced endotoxaemia model in mice and rats. LPS (10 mg\/kg; from Salmonella Typhosa) was intraperitoneally injected into mice and rats. Animals of every species were divided into five groups and sacrificed at specific points in time (0, 3, 6, 9, 12 h). White blood cells (WBC) decreased significantly in both species after 3 h and partially recovered with time, whereas platelet decrease did not recover. Oxidative burst and iNOS-derived nitrosyl-iron hemoglobin (HbNO) increased with time (maxima at 9 or 12 h). Immune cell infiltration (CD68 and F4\/80 content) showed an increase with time, which was supported by increased vascular mRNA expression of VCAM-1, P-selectin, IL-6 and TNF-\u03b1. We characterized the time responses of vascular inflammation and oxidative\/nitrosative stress in LPS-induced endotoxaemic mice and rats. The results of this study will help to interpret and compare data from different animal species in LPS-induced endotoxaemia models for the identification of new drug targets.<\/jats:p>","DOI":"10.3390\/ijms18102176","type":"journal-article","created":{"date-parts":[[2017,10,18]],"date-time":"2017-10-18T11:10:00Z","timestamp":1508325000000},"page":"2176","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Time Response of Oxidative\/Nitrosative Stress and Inflammation in LPS-Induced Endotoxaemia\u2014A Comparative Study of Mice and Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Sebastian","family":"Steven","sequence":"first","affiliation":[{"name":"Center for Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6507-0339","authenticated-orcid":false,"given":"Mobin","family":"Dib","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyer","family":"Roohani","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Kashani","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5503-4150","authenticated-orcid":false,"given":"Thomas","family":"M\u00fcnzel","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Daiber","sequence":"additional","affiliation":[{"name":"Center for Cardiology, Cardiology I, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"},{"name":"Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, D-55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1007\/s00134-015-3906-y","article-title":"The surviving sepsis campaign bundles and outcome: Results from the international multicentre prevalence study on sepsis (the impress study)","volume":"41","author":"Rhodes","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_2","first-page":"1","article-title":"Inpatient care for septicemia or sepsis: A challenge for patients and hospitals","volume":"62","author":"Hall","year":"2011","journal-title":"NCHS Data Brief"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"i1585","DOI":"10.1136\/bmj.i1585","article-title":"Sepsis: Pathophysiology and clinical management","volume":"353","author":"Gotts","year":"2016","journal-title":"BMJ"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1097\/00003246-199607000-00010","article-title":"Sir isaac newton, sepsis, sirs, and cars","volume":"24","author":"Bone","year":"1996","journal-title":"Crit. Care Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1073\/pnas.1401965111","article-title":"Genomic responses in mouse models greatly mimic human inflammatory diseases","volume":"112","author":"Takao","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/cvr\/cvs246","article-title":"Glucose-independent improvement of vascular dysfunction in experimental sepsis by dipeptidyl-peptidase 4 inhibition","volume":"96","author":"Knorr","year":"2012","journal-title":"Cardiovasc. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18185","DOI":"10.3390\/ijms160818185","article-title":"Exploiting the pleiotropic antioxidant effects of established drugs in cardiovascular disease","volume":"16","author":"Steven","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1111\/bph.13549","article-title":"Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice","volume":"174","author":"Steven","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s00395-015-0465-x","article-title":"Gliptin and glp-1 analog treatment improves survival and vascular inflammation\/dysfunction in animals with lipopolysaccharide-induced endotoxemia","volume":"110","author":"Steven","year":"2015","journal-title":"Basic Res. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: Differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.etp.2005.10.002","article-title":"Clinical chemistry and haematology historical data in control sprague-dawley rats from pre-clinical toxicity studies","volume":"57","author":"Petterino","year":"2006","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1177\/0300985811429314","article-title":"Immunological variation between inbred laboratory mouse strains: Points to consider in phenotyping genetically immunomodified mice","volume":"49","author":"Sellers","year":"2012","journal-title":"Vet. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1097\/00024382-200210000-00009","article-title":"Genetic contribution to the septic response in a mouse model","volume":"18","author":"Stewart","year":"2002","journal-title":"Shock"},{"key":"ref_16","first-page":"147","article-title":"Recent insights into the pathogenesis of bacterial sepsis","volume":"68","author":"Anas","year":"2010","journal-title":"Neth. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1056\/NEJMoa1401520","article-title":"Rosuvastatin for sepsis-associated acute respiratory distress syndrome","volume":"370","author":"Truwit","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_18","first-page":"223","article-title":"Redox signalling in endothelial cells\u2014Novel mechanisms explaining endothelium function and dysfunction in health, disease and aging","volume":"18","author":"Bachschmid","year":"2003","journal-title":"BIF futura"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2258","DOI":"10.1016\/j.peptides.2006.03.025","article-title":"Time-dependent expression of renal vaso-regulatory molecules in lps-induced endotoxemia in rat","volume":"27","author":"Yamaguchi","year":"2006","journal-title":"Peptides"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"R323","DOI":"10.1186\/cc3532","article-title":"Time course of endothelial damage in septic shock: Prediction of outcome","volume":"9","author":"Hein","year":"2005","journal-title":"Crit. Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1479-5876-9-23","article-title":"Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: A prospective study","volume":"9","author":"Alves","year":"2011","journal-title":"J. Transl. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R129","DOI":"10.1186\/cc9097","article-title":"Time course of nitric oxide synthases, nitrosative stress, and poly(adp ribosylation) in an ovine sepsis model","volume":"14","author":"Lange","year":"2010","journal-title":"Crit. Care"},{"key":"ref_23","first-page":"37","article-title":"Relationship between leukotriene b4 and prostaglandin i2 in patients with sepsis","volume":"86","author":"Nakae","year":"1994","journal-title":"Res. Commun. Mol. Pathol. Pharmacol."},{"key":"ref_24","first-page":"291","article-title":"Prostacyclin and thromboxane a2 in septic shock: Species differences","volume":"20","author":"Yellin","year":"1986","journal-title":"Circ. Shock"},{"key":"ref_25","first-page":"133","article-title":"Thromboxane and prostacyclin production during septic shock","volume":"7","author":"Butler","year":"1982","journal-title":"Adv. Shock Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/0735-6757(84)90107-4","article-title":"The potential role of thromboxane and prostacyclin in endotoxic and septic shock","volume":"2","author":"Cook","year":"1984","journal-title":"Am. J. Emerg. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.bbrc.2005.12.009","article-title":"Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in lps-stimulated raw 264.7 macrophages","volume":"340","author":"Schildknecht","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.niox.2006.02.003","article-title":"Mechanisms underlying dysfunction of carotid arteries in genetically hyperlipidemic rabbits","volume":"15","author":"August","year":"2006","journal-title":"Nitric Oxide"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1161\/01.ATV.17.9.1746","article-title":"Inhibition of inducible nitric oxide synthase restores endothelium-dependent relaxations in proinflammatory mediator-induced blood vessels","volume":"17","author":"Kessler","year":"1997","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1160\/TH08-03-0192","article-title":"Thromboembolic complications of sepsis: What is the incidence and pathophysiological mechanisms involved?","volume":"99","author":"Holub","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13054-015-0931-8","article-title":"Association between trends in clinical variables and outcome in intensive care patients with faecal peritonitis: Analysis of the genosept cohort","volume":"19","author":"Tridente","year":"2015","journal-title":"Crit. Care"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1161\/HYPERTENSIONAHA.108.112029","article-title":"Activation of the pgi(2)\/ip system contributes to the development of circulatory failure in a rat model of endotoxic shock","volume":"52","author":"Hocherl","year":"2008","journal-title":"Hypertension"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s00210-010-0559-9","article-title":"Glp-1 signaling preserves cardiac function in endotoxemic fischer 344 and dpp4-deficient rats","volume":"382","author":"Ku","year":"2010","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1152\/physrev.00029.2006","article-title":"Nitric oxide and peroxynitrite in health and disease","volume":"87","author":"Pacher","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/SHK.0b013e3181e7e9ba","article-title":"Pathophysiological roles of peroxynitrite in circulatory shock","volume":"34","author":"Szabo","year":"2010","journal-title":"Shock"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.freeradbiomed.2003.10.012","article-title":"Measurement of nad(p)h oxidase-derived superoxide with the luminol analogue l-012","volume":"36","author":"Daiber","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1124\/jpet.108.149716","article-title":"Monitoring white blood cell mitochondrial aldehyde dehydrogenase activity: Implications for nitrate therapy in humans","volume":"330","author":"Wenzel","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1007\/s00395-013-0386-5","article-title":"Cd40l contributes to angiotensin ii-induced pro-thrombotic state, vascular inflammation, oxidative stress and endothelial dysfunction","volume":"108","author":"Hausding","year":"2013","journal-title":"Basic Res. Cardiol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2176\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:47:45Z","timestamp":1760208465000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/18\/10\/2176"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,18]]},"references-count":38,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["ijms18102176"],"URL":"https:\/\/doi.org\/10.3390\/ijms18102176","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,18]]}}}