{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:25:55Z","timestamp":1787243155399,"version":"build-2736575974"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Mitochondrial ROS (mitoROS) control many reactions in cells. Biological effects of mitoROS in vivo can be investigated by modulation via mitochondria-targeted antioxidants (mtAOX, mitoTEMPO). The aim of this study was to determine how mitoROS influence redox reactions in different body compartments in a rat model of endotoxemia. We induced inflammatory response by lipopolysaccharide (LPS) injection and analyzed effects of mitoTEMPO in blood, abdominal cavity, bronchoalveolar space, and liver tissue. MitoTEMPO decreased the liver damage marker aspartate aminotransferase; however, it neither influenced the release of cytokines (e.g., tumor necrosis factor, IL-4) nor decreased ROS generation by immune cells in the compartments examined. In contrast, ex vivo mitoTEMPO treatment substantially reduced ROS generation. Examination of liver tissue revealed several redox paramagnetic centers sensitive to in vivo LPS and mitoTEMPO treatment and high levels of nitric oxide (NO) in response to LPS. NO levels in blood were lower than in liver, and were decreased by in vivo mitoTEMPO treatment. Our data suggest that (i) inflammatory mediators are not likely to directly contribute to ROS-mediated liver damage and (ii) mitoTEMPO is more likely to affect the redox status of liver cells reflected in a redox change of paramagnetic molecules. Further studies are necessary to understand these mechanisms.<\/jats:p>","DOI":"10.3390\/biom13050794","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T09:18:09Z","timestamp":1683278289000},"page":"794","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of mitoTEMPO on Redox Reactions in Different Body Compartments upon Endotoxemia in Rats"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2759-211X","authenticated-orcid":false,"given":"Adelheid","family":"Weidinger","sequence":"first","affiliation":[{"name":"Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-4374","authenticated-orcid":false,"given":"Andras T.","family":"Meszaros","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria"},{"name":"Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergiu","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-4997","authenticated-orcid":false,"given":"Andrey V.","family":"Kozlov","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Traumatology, The Research Center in Cooperation with AUVA, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jarczak, D., and Nierhaus, A. (2022). Cytokine Storm\u2014Definition, Causes, and Implications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911740"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1089\/ars.2014.5996","article-title":"Vicious Inducible Nitric Oxide Synthase-Mitochondrial Reactive Oxygen Species Cycle Accelerates Inflammatory Response and Causes Liver Injury in Rats","volume":"22","author":"Weidinger","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.redox.2017.05.017","article-title":"Mitochondria-Meditated Pathways of Organ Failure upon Inflammation","volume":"13","author":"Kozlov","year":"2017","journal-title":"Redox Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF01515994","article-title":"Solution of the Problem of Energy Coupling in Terms of Chemiosmotic Theory","volume":"3","author":"Skulachev","year":"1972","journal-title":"J. Bioenerg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1113\/jphysiol.2003.049478","article-title":"Mitochondrial Formation of Reactive Oxygen Species","volume":"552","author":"Turrens","year":"2003","journal-title":"J. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20081386","article-title":"How Mitochondria Produce Reactive Oxygen Species","volume":"417","author":"Murphy","year":"2009","journal-title":"Biochem. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1002\/mnfr.200900386","article-title":"V Tocopheryl Quinones and Mitochondria","volume":"54","author":"Gille","year":"2010","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/jlb.61.6.647","article-title":"Mechanisms of Neutrophil-Induced Parenchymal Cell Injury","volume":"61","author":"Jaeschke","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ajpath.2011.10.001","article-title":"LPS-Induced Murine Systemic Inflammation Is Driven by Parenchymal Cell Activation and Exclusively Predicted by Early MCP-1 Plasma Levels","volume":"180","author":"Juskewitch","year":"2012","journal-title":"Am. J. Pathol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1901298","DOI":"10.1183\/13993003.01298-2019","article-title":"Human Lipopolysaccharide Models Provide Mechanistic and Therapeutic Insights into Systemic and Pulmonary Inflammation","volume":"56","author":"Brooks","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1097\/SHK.0000000000001242","article-title":"Part II: Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) for Types of Infections and Organ Dysfunction Endpoints","volume":"51","author":"Libert","year":"2019","journal-title":"Shock"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/S0171-2985(11)80346-3","article-title":"Agonists and Antagonists for Lipopolysaccharide-Induced Cytokines","volume":"187","author":"Flad","year":"1993","journal-title":"Immunobiology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"L899","DOI":"10.1152\/ajplung.00338.2002","article-title":"Mechanisms of Bacterial Lipopolysaccharide-Induced Endothelial Apoptosis","volume":"284","author":"Bannerman","year":"2003","journal-title":"Am. J. Physiol.\u2014Lung Cell. Mol. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1097\/00005344-199500252-00002","article-title":"Lipopolysaccharide Signal Transduction, Regulation of Tumor Necrosis Factor Biosynthesis, and Signaling by Tumor Necrosis Factor Itself","volume":"25","author":"Beutler","year":"1995","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fphys.2013.00138","article-title":"Experimental Data Suggesting That Inflammation Mediated Rat Liver Mitochondrial Dysfunction Results from Secondary Hypoxia Rather than from Direct Effects of Inflammatory Mediators","volume":"4","author":"Weidinger","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-1-0716-1605-5_14","article-title":"Characterization of Paramagnetic Iron-Sulfur Clusters Using Electron Paramagnetic Resonance Spectroscopy","volume":"2353","author":"Stich","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101566","DOI":"10.1016\/j.redox.2020.101566","article-title":"Electron Paramagnetic Resonance Spectroscopy Reveals Alterations in the Redox State of Endogenous Copper and Iron Complexes in Photodynamic Stress-Induced Ischemic Mouse Liver","volume":"34","author":"Jakubowska","year":"2020","journal-title":"Redox Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0891-5849(92)90159-E","article-title":"Intracellular Free Iron in Liver Tissue and Liver Homogenate: Studies with Electron Paramagnetic Resonance on the Formation of Paramagnetic Complexes with Desferal and Nitric Oxide","volume":"13","author":"Kozlov","year":"1992","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2372","DOI":"10.1002\/mrm.26291","article-title":"EPR Analysis of Extra- and Intracellular Nitric Oxide in Liver Biopsies","volume":"77","author":"Dumitrescu","year":"2017","journal-title":"Magn. Reson. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.freeradbiomed.2006.05.001","article-title":"The Measurement of Blood and Plasma Nitrite by Chemiluminescence: Pitfalls and Solutions","volume":"41","author":"Pelletier","year":"2006","journal-title":"Free Radic. Biol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"203","DOI":"10.5487\/TR.2010.26.3.203","article-title":"Standardization of Bronchoalveolar Lavage Method Based on Suction Frequency Number and Lavage Fraction Number Using Rats","volume":"26","author":"Song","year":"2010","journal-title":"Toxicol. Res."},{"key":"ref_22","first-page":"1488","article-title":"Isolation of Mouse Peritoneal Cavity Cells","volume":"35","author":"Ray","year":"2010","journal-title":"J. Vis. Exp."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1086\/314717","article-title":"Dose-Related Inflammatory Effects of Intravenous Endotoxin in Humans: Evaluation of a New Clinical Lot of Escherichia Coli O:113 Endotoxin","volume":"179","author":"Suffredini","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1080\/08923970802135146","article-title":"Pretreatment of Mice with Rifampicin Prolongs Survival of Endotoxic Shock by Modulating the Levels of Inflammatory Cytokines","volume":"30","author":"An","year":"2008","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/ars.2012.5149","article-title":"Reactive Oxygen Species in Inflammation and Tissue Injury","volume":"20","author":"Mittal","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Weidinger, A., Birgisd\u00f3ttir, L., Sch\u00e4ffer, J., Meszaros, A.T., Zavadskis, S., M\u00fcllebner, A., Hecker, M., Duvigneau, J.C., Sommer, N., and Kozlov, A.V. (2022). Systemic Effects of MitoTEMPO upon Lipopolysaccharide Challenge Are Due to Its Antioxidant Part, While Local Effects in the Lung Are Due to Triphenylphosphonium. Antioxidants, 11.","DOI":"10.3390\/antiox11020323"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1111\/eci.12069","article-title":"Mitochondrial Function in Sepsis","volume":"43","author":"Jeger","year":"2013","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"G543","DOI":"10.1152\/ajpgi.00331.2005","article-title":"Different Effects of Endotoxic Shock on the Respiratory Function of Liver and Heart Mitochondria in Rats","volume":"290","author":"Kozlov","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s10753-010-9185-4","article-title":"Peritoneal Inflammation in Pigs Is Associated with Early Mitochondrial Dysfunction in Liver and Kidney","volume":"33","author":"Kozlov","year":"2010","journal-title":"Inflammation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"688","DOI":"10.3748\/wjg.v6.i5.688","article-title":"Effect of Hepatocyte Apoptosis Induced by TNF-\u03b1 on Acute Severe Hepatitis in Mouse Models","volume":"6","author":"Zang","year":"2000","journal-title":"World J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating Mitochondrial DAMPs Cause Inflammatory Responses to Injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"R1134","DOI":"10.1152\/ajpregu.00842.2010","article-title":"Mitochondrial Reactive Oxygen Species and Calcium Uptake Regulate Activation of Phagocytic NADPH Oxidase","volume":"302","author":"Dikalov","year":"2012","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1089\/ars.2012.4953","article-title":"Molecular Mechanisms of the Crosstalk between Mitochondria and NADPH Oxidase through Reactive Oxygen Species-Studies in White Blood Cells and in Animal Models","volume":"20","author":"Steven","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3389\/fcimb.2017.00373","article-title":"Neutrophils to the ROScue: Mechanisms of NADPH Oxidase Activation and Bacterial Resistance","volume":"7","author":"Nguyen","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/5\/794\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:29:44Z","timestamp":1760124584000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/5\/794"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,5]]},"references-count":34,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["biom13050794"],"URL":"https:\/\/doi.org\/10.3390\/biom13050794","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,5]]}}}