{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:03:58Z","timestamp":1760241838516,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T00:00:00Z","timestamp":1535587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Background aim: Reperfusion after hemorrhagic traumatic shock (HTS) is often associated with complications that are partly ascribed to the formation of reactive oxygen species (ROS). The aim of our study was to compare the effects of restrictive reperfusion (RR) to rapid full reperfusion (FR) on ROS formation and\/or oxidative events. Materials and methods: Anesthetized male rats were randomly subjected to HTS followed by FR (75 mL\/kg\/h) or RR (30 mL\/kg\/h for 40 min, followed by 75 mL\/kg\/h) with Ringer\u2019s solution (n = 8\/group). Compartment-specific ROS formation was determined by infusion of ROS scavenger 1-hydroxy-3-carboxy-2,2,5,5-tetramethyl-pyrrolidine hydrochloride (CP-H) during resuscitation, followed by electron paramagnetic resonance spectroscopy. Sham-operated animals (n = 8) served as controls. The experiment was terminated 100 min post-shock. Results: Mean arterial pressure was significantly higher in the FR compared to the RR group during early reperfusion. Only RR animals, not FR animals, showed significantly higher ROS concentrations in erythrocytes (1951 \u00b1 420 vs. 724 \u00b1 75 AU) and in liver (474 \u00b1 57 vs. 261 \u00b1 21 AU) compared to sham controls. This was accompanied by elevated alanine aminotransferase and creatinine levels in RR animals compared to both shams and FR animals, while lipid peroxidation products (thiobarbituric acid reactive substances) were significantly increased only in the kidney in the FR group (p &lt; 0.05). RR animals showed significantly higher plasma peroxiredoxin-4 values when compared to the FR group (20 \u00b1 2 vs. 14 \u00b1 0.5 RLU). Conclusion: Restrictive reperfusion after HTS is associated with increased ROS formation in erythrocytes and liver compared to sham controls. Moreover, the restrictive reperfusion is associated with a more pronounced injury to the liver and kidney, which is likely mediated by other than lipid peroxidation process and\/or oxidative stress reactions.<\/jats:p>","DOI":"10.3390\/molecules23092195","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T10:30:06Z","timestamp":1535625006000},"page":"2195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Organ-Specific Oxidative Events under Restrictive Versus Full Reperfusion Following Hemorrhagic Traumatic Shock in Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Carina","family":"Penzenstadler","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center for Traumatology, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Zifko","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center for Traumatology, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Jafarmadar","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center for Traumatology, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janin","family":"Schulte","sequence":"additional","affiliation":[{"name":"Thermo Fisher Scientific, BRAHMS Biomarkers, Research Department, 16761 Hennigsdorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Struck","sequence":"additional","affiliation":[{"name":"Thermo Fisher Scientific, BRAHMS Biomarkers, Research Department, 16761 Hennigsdorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Stainer","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center for Traumatology, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-4997","authenticated-orcid":false,"given":"Andrey","family":"Kozlov","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center for Traumatology, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soheyl","family":"Bahrami","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center for Traumatology, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/cc3779","article-title":"The epidemiology and modern management of traumatic hemorrhage: US and international perspectives","volume":"9","author":"Kauvar","year":"2005","journal-title":"Crit. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1007\/s004230100242","article-title":"Molecular mechanisms in the early phase of hemorrhagic shock","volume":"386","author":"Hierholzer","year":"2001","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1097\/SHK.0b013e3181c30f0c","article-title":"Fluid resuscitation: Past, present, and the future","volume":"33","author":"Santry","year":"2010","journal-title":"Shock"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1177\/1538574407304510","article-title":"Reperfusion syndrome: Cellular mechanisms of microvascular dysfunction and potential therapeutic strategies","volume":"41","author":"Girn","year":"2007","journal-title":"Vasc. Endovasc. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1016\/S0041-1345(02)03471-1","article-title":"The molecular events underlying ischemia\/reperfusion injury","volume":"34","year":"2002","journal-title":"Transplant. Proc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1097\/01.shk.0000208808.03148.ea","article-title":"Small-volume fluid resuscitation with hypertonic saline prevents inflammation but not mortality in a rat model of hemorrhagic shock","volume":"25","author":"Bahrami","year":"2006","journal-title":"Shock"},{"key":"ref_7","first-page":"798","article-title":"Experimental study of controlled fluid resuscitation in the treatment of severe and uncontrolled hemorrhagic shoc","volume":"63","author":"Lu","year":"2007","journal-title":"J. Trauma"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1097\/01.SHK.0000094036.09886.9b","article-title":"Splanchnic perfusion during delayed, hypotensive, or aggressive fluid resuscitation from uncontrolled hemorrhage","volume":"20","author":"Varela","year":"2003","journal-title":"Shock"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1097\/SHK.0b013e3181d8e578","article-title":"Rons formation under restrictive reperfusion does not affect organ dysfunction early after hemorrhage and trauma","volume":"34","author":"Zifko","year":"2010","journal-title":"Shock"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.cca.2010.05.016","article-title":"Immunoluminometric assay for quantification of peroxiredoxin 4 in human serum","volume":"411","author":"Schulte","year":"2010","journal-title":"Clin. Chim. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0160-5402(85)90029-4","article-title":"Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium","volume":"14","author":"Mullane","year":"1985","journal-title":"J. Pharmacol. Methods"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Nanduri, J., Vaddi, D.R., Khan, S.A., Wang, N., Makerenko, V., and Prabhakar, N.R. (2013). Xanthine oxidase mediates hypoxia-inducible factor-2alpha degradation by intermittent hypoxia. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075838"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.freeradbiomed.2015.08.012","article-title":"The cytoprotective effect of nitrite is based on the formation of dinitrosyl iron complexes","volume":"89","author":"Dungel","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1097\/ALN.0b013e3181c4a5e2","article-title":"Fluid resuscitation does not improve renal oxygenation during hemorrhagic shock in rats","volume":"112","author":"Legrand","year":"2010","journal-title":"Anesthesiology"},{"key":"ref_15","first-page":"144","article-title":"Effect of decreased perfusion pressure on glomerular permeability in the rat","volume":"57","author":"Weening","year":"1987","journal-title":"Lab. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/SHK.0b013e3181aef322","article-title":"Reperfusion does not induce oxidative stress but sustained endoplasmic reticulum stress in livers of rats subjected to traumatic-hemorrhagic shock","volume":"33","author":"Duvigneau","year":"2010","journal-title":"Shock"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2007.12.025","article-title":"Free radical metabolism in human erythrocytes","volume":"390","author":"Cimen","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1042\/bj2490185","article-title":"Formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Is haemoglobin a biological Fenton reagent?","volume":"249","author":"Puppo","year":"1988","journal-title":"Biochem. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.jbchem.a022632","article-title":"Peroxiredoxin IV is a secretable protein with heparin-binding properties under reduced conditions","volume":"127","author":"Matsumoto","year":"2000","journal-title":"J. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0968-0004(02)00003-8","article-title":"Structure, mechanism and regulation of peroxiredoxins","volume":"28","author":"Wood","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/SHK.0b013e3182115f40","article-title":"Circulating levels of peroxiredoxin 4 as a novel biomarker of oxidative stress in patients with sepsis","volume":"35","author":"Schulte","year":"2011","journal-title":"Shock"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/j.biocel.2012.04.008","article-title":"Structural and functional analysis of native peroxiredoxin 2 in human red blood cells","volume":"44","author":"Ogasawara","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e002956","DOI":"10.1161\/JAHA.112.002956","article-title":"Peroxiredoxin 4, a novel circulating biomarker for oxidative stress and the risk of incident cardiovascular disease and all-cause mortality","volume":"1","author":"Abbasi","year":"2012","journal-title":"J. Am. Heart Assoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cellsig.2017.01.007","article-title":"A positive feedback loop between ROS and Mxi1-0 promotes hypoxia-induced VEGF expression in human hepatocellular carcinoma cells","volume":"31","author":"Hu","year":"2017","journal-title":"Cell Signal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.freeradbiomed.2016.09.025","article-title":"Lack of mitochondrial DNA impairs chemical hypoxia-induced autophagy in liver tumor cells through ROS-AMPK-ULK1 signaling dysregulation independently of HIF-1\u03b1","volume":"101","author":"Marin","year":"2016","journal-title":"Free Radic. Biol. Med."},{"key":"ref_26","first-page":"243","article-title":"Hemorrhage- and resuscitation-related alterations in gastrointestinal circulation: Effect of a low dose of L-NMMA","volume":"23","author":"Sobhian","year":"2005","journal-title":"Shock"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/9\/2195\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:22:12Z","timestamp":1760196132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/23\/9\/2195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,30]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2018,9]]}},"alternative-id":["molecules23092195"],"URL":"https:\/\/doi.org\/10.3390\/molecules23092195","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2018,8,30]]}}}