{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:46:06Z","timestamp":1793335566861,"version":"4.5.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T00:00:00Z","timestamp":1628726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015763","name":"Szegedi Tudom\u00e1nyegyetem","doi-asserted-by":"publisher","award":["5312"],"award-info":[{"award-number":["5312"]}],"id":[{"id":"10.13039\/501100015763","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>The systemic host response in sepsis is frequently accompanied by central nervous system (CNS) dysfunction. Evidence suggests that excessive formation of neutrophil extracellular traps (NETs) can increase the permeability of the blood\u2013brain barrier (BBB) and that the evolving mitochondrial damage may contribute to the pathogenesis of sepsis-associated encephalopathy. Kynurenic acid (KYNA), a metabolite of tryptophan catabolism, exerts pleiotropic cell-protective effects under pro-inflammatory conditions. Our aim was to investigate whether exogenous KYNA or its synthetic analogues SZR-72 and SZR-104 affect BBB permeability secondary to NET formation and influence cerebral mitochondrial disturbances in a clinically relevant rodent model of intraabdominal sepsis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sprague\u2013Dawley rats were subjected to fecal peritonitis (0.6\u00a0g kg<jats:sup>-1<\/jats:sup> ip) or a sham operation. Septic animals were treated with saline or KYNA, SZR-72 or SZR-104 (160 \u00b5mol kg<jats:sup>-1<\/jats:sup> each ip) 16h and 22h after induction. Invasive monitoring was performed on anesthetized animals to evaluate respiratory, cardiovascular, renal, hepatic and metabolic parameters to calculate rat organ failure assessment (ROFA) scores. NET components (citrullinated histone H3 (CitH3); myeloperoxidase (MPO)) and the NET inducer IL-1\u03b2, as well as IL-6 and a brain injury marker (S100B) were detected from plasma samples. After 24h, leukocyte infiltration (tissue MPO) and mitochondrial complex I- and II-linked (CI\u2013CII) oxidative phosphorylation (OXPHOS) were evaluated. In a separate series, Evans Blue extravasation and the edema index were used to assess BBB permeability in the same regions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sepsis was characterized by significantly elevated ROFA scores, while the increased BBB permeability and plasma S100B levels demonstrated brain damage. Plasma levels of CitH3, MPO and IL-1\u03b2 were elevated in sepsis but were ameliorated by KYNA and its synthetic analogues. The sepsis-induced deterioration in tissue CI\u2013CII-linked OXPHOS and BBB parameters as well as the increase in tissue MPO content were positively affected by KYNA\/KYNA analogues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study is the first to report that KYNA and KYNA analogues are potential neuroprotective agents in experimental sepsis. The proposed mechanistic steps involve reduced peripheral NET formation, lowered BBB permeability changes and alleviation of mitochondrial dysfunction in the CNS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.717157","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:10:09Z","timestamp":1628763009000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":48,"title":["Kynurenic Acid and Its Synthetic Derivatives Protect Against Sepsis-Associated Neutrophil Activation and Brain Mitochondrial Dysfunction in Rats"],"prefix":"10.3389","volume":"12","author":[{"given":"Marietta Z.","family":"Poles","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"N\u00e1szai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Gul\u00e1csi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint L.","family":"Czak\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n G.","family":"G\u00e1l","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy J.","family":"Glenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dishana","family":"Dookhun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Rutai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs P.","family":"Tall\u00f3sy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1lint","family":"L\u0151rinczi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Szatm\u00e1ri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"F\u00fcl\u00f6p","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"V\u00e9csei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mih\u00e1ly","family":"Boros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e1szl\u00f3","family":"Juh\u00e1sz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Kaszaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17165852","article-title":"Sepsis-Associated Brain Dysfunction: A Review of Current Literature","volume":"17","author":"Czempik","year":"2020","journal-title":"Int J Environ Res Public Health"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2015.04.062","article-title":"Sepsis-Induced Brain Mitochondrial Dysfunction is Associated With Altered Mitochondrial Src and PTP1B Levels","volume":"1620","author":"Lyu","year":"2015","journal-title":"Brain Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/2110-5820-3-15","article-title":"Understanding Brain Dysfunction in Sepsis","volume":"3","author":"Sonneville","year":"2013","journal-title":"Ann Intensive Care"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1042\/CS19980327","article-title":"Faecal Peritonitis Causes Oedema and Neuronal Injury in Pig Cerebral Cortex","volume":"96","author":"Papadopoulos","year":"1999","journal-title":"Clin Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.2002.00065.x","article-title":"Blood-Brain Barrier Breakdown in Septic Encephalopathy and Brain Tumours","volume":"200","author":"Davies","year":"2002","journal-title":"J Anat"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2005.12.001","article-title":"Perimicrovascular Edema in the Frontal Cortex in a Rat Model of Intraperitoneal Sepsis","volume":"198","author":"Ari","year":"2006","journal-title":"Exp Neurol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.09.162","article-title":"Hippocampus and Cerebellum Damage in Sepsis Induced by Lipopolysaccharide in Aged Rats - Pregabalin can Prevent Damage","volume":"108","author":"Aslankoc","year":"2018","journal-title":"BioMed Pharmacother"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e31820d94a5","article-title":"Neutrophil Depletion Reduces Blood-Brain Barrier Breakdown, Axon Injury, and Inflammation After Intracerebral Hemorrhage","volume":"70","author":"Moxon-Emre","year":"2011","journal-title":"J Neuropathol Exp Neurol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385","article-title":"Neutrophil Extracellular Traps Kill Bacteria","volume":"303","author":"Brinkmann","year":"2004","journal-title":"Science"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121477","article-title":"The Brain Entangled: The Contribution of Neutrophil Extracellular Traps to the Diseases of the Central Nervous System","volume":"8","author":"Manda-Handzlik","year":"2019","journal-title":"Cells"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-04-457671","article-title":"Netosis: How Vital is it","volume":"122","author":"Yipp","year":"2013","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.105","article-title":"Neutrophil Extracellular Traps in Immunity and Disease","volume":"18","author":"Papayannopoulos","year":"2018","journal-title":"Nat Rev Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13112","article-title":"Neutrophil Dysregulation During Sepsis: An Overview and Update","volume":"21","author":"Shen","year":"2017","journal-title":"J Cell Mol Med"},{"key":"B15","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.cmet.2019.06.005","article-title":"A Breakdown in Metabolic Reprogramming Causes Microglia Dysfunction in Alzheimer\u2019s Disease","volume":"30","author":"Baik","year":"2019","journal-title":"Cell Metab"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2008.07.002","article-title":"Mitochondrial Respiratory Chain and Creatine Kinase Activities in Rat Brain After Sepsis Induced by Cecal Ligation and Perforation","volume":"8","author":"Comim","year":"2008","journal-title":"Mitochondrion"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2020.566582","article-title":"Divergent Effects of the N-Methyl-D-Aspartate Receptor Antagonist Kynurenic Acid and the Synthetic Analog SZR-72 on Microcirculatory and Mitochondrial Dysfunction in Experimental Sepsis","volume":"7","author":"Juh\u00e1sz","year":"2020","journal-title":"Front Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2015.6407","article-title":"The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases","volume":"23","author":"Nakahira","year":"2015","journal-title":"Antioxid Redox Signal"},{"key":"B19","doi-asserted-by":"publisher","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":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21686","article-title":"Late Brain Alterations in Sepsis-Survivor Rats","volume":"67","author":"Steckert","year":"2013","journal-title":"Synapse"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000547","article-title":"Effect of Histone Acetylation on N-methyl-D-aspartate 2B Receptor Subunits and Interleukin-1 Receptors in Association With Nociception-Related Somatosensory Cortex Dysfunction in a Mouse Model of Sepsis","volume":"45","author":"Imamura","year":"2016","journal-title":"Shock"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e0188273","DOI":"10.1371\/journal.pone.0188273","article-title":"Sepsis-Induced Selective Loss of NMDA Receptors Modulates Hippocampal Neuropathology in Surviving Septic Mice","volume":"12","author":"Zhang","year":"2017","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/nrd3793","article-title":"Kynurenines in the CNS: Recent Advances and New Questions","volume":"12","author":"V\u00e9csei","year":"2013","journal-title":"Nat Rev Drug Discov"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2012.06.044","article-title":"N-methyl-D-aspartate Receptor Antagonist Therapy Suppresses Colon Motility and Inflammatory Activation Six Days After the Onset of Experimental Colitis in Rats","volume":"691","author":"\u00c9rces","year":"2012","journal-title":"Eur J Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25030564","article-title":"Are Kynurenines Accomplices or Principal Villains in Dementia? Maintenance of Kynurenine Metabolism","volume":"25","author":"Tanaka","year":"2020","journal-title":"Molecules"},{"key":"B26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1097\/SHK.0000000000001414","article-title":"Endothelin A and B Receptors: Potential Targets for Microcirculatory-Mitochondrial Therapy in Experimental Sepsis","volume":"54","author":"Rutai","year":"2020","journal-title":"Shock"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2174\/092986709789909602","article-title":"Syntheses, Transformations and Pharmaceutical Applications of Kynurenic Acid Derivatives","volume":"16","author":"F\u00fcl\u00f6p","year":"2009","journal-title":"Curr Med Chem"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13010061","article-title":"Szr-104, a Novel Kynurenic Acid Analogue With High Permeability Through the Blood-Brain Barrier","volume":"13","author":"Moln\u00e1r","year":"2021","journal-title":"Pharmaceutics"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001212","article-title":"Minimum Quality Threshold in Pre-Clinical Sepsis Studies (Mqtipss): An International Expert Consensus Initiative for Improvement of Animal Modeling in Sepsis","volume":"50","author":"Osuchowski","year":"2018","journal-title":"Shock"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2020.111063","article-title":"Aging Influences in the Blood-Brain Barrier Permeability and Cerebral Oxidative Stress in Sepsis","volume":"140","author":"Margotti","year":"2020","journal-title":"Exp Gerontol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1056\/NEJM199607183350313","article-title":"Measurement of Neutrophil Content in Brain and Lung Tissue by a Modified Myeloperoxidase Assay","volume":"16","author":"Kuebler","year":"1996","journal-title":"Int J Microcirc"},{"key":"B32","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.brainres.2011.04.003","article-title":"Effects of NMDA Receptor Modulators on a Blood-Brain Barrier In Vitro Model","volume":"1394","author":"Neuhaus","year":"2011","journal-title":"Brain Res"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0969-19.2019","article-title":"Nonionotropic Action of Endothelial NMDA Receptors on Blood-Brain Barrier Permeability Via Rho\/ROCK-mediated Phosphorylation of Myosin","volume":"40","author":"Mehra","year":"2020","journal-title":"J Neurosci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3913","article-title":"Neutrophils Promote Alzheimer\u2019s Disease-Like Pathology and Cognitive Decline Via LFA-1 Integrin","volume":"21","author":"Zenaro","year":"2015","journal-title":"Nat Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/s13054-019-2407-8","article-title":"Neutrophil Extracellular Traps (Nets) Exacerbate Severity of Infant Sepsis","volume":"23","author":"Col\u00f3n","year":"2019","journal-title":"Crit Care"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e0182587","DOI":"10.1371\/journal.pone.0182587","article-title":"Neutrophil Extracellular Trap (NET) Levels in Human Plasma are Associated With Active TB","volume":"12","author":"Schechter","year":"2017","journal-title":"PloS One"},{"key":"B37","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.trsl.2021.02.003","article-title":"Histone Citrullination as a Novel Biomarker and Target to Inhibit Progression of Abdominal Aortic Aneurysms","volume":"233","author":"Eilenberg","year":"2021","journal-title":"Transl Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"fj201800691R","DOI":"10.1096\/fj.201800691R","article-title":"Peptidylarginine Deiminase 4: A Nuclear Button Triggering Neutrophil Extracellular Traps in Inflammatory Diseases and Aging","volume":"32","author":"Wong","year":"2018","journal-title":"FASEB J"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02957","article-title":"Citrullinated Histone H3 as a Therapeutic Target for Endotoxic Shock in Mice","volume":"10","author":"Deng","year":"2020","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.314571","article-title":"Plasma Peptidylarginine Deiminase Iv Promotes Vwf-Platelet String Formation and Accelerates Thrombosis After Vessel Injury","volume":"125","author":"Sorvillo","year":"2019","journal-title":"Circ Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13717","article-title":"Peptidylarginine Deiminase 4 Concentration, But Not PADI4 Polymorphisms, Is Associated With ICU Mortality in Septic Shock Patients","volume":"22","author":"Costa","year":"2018","journal-title":"J Cell Mol Med"},{"key":"B42","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1007\/s15010-020-01528-y","article-title":"Serum Citrullinated Histone H3 Concentrations Differentiate Patients With Septic Verses non-Septic Shock and Correlate With Disease Severity","volume":"49","author":"Tian","year":"2021","journal-title":"Infection"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01406","article-title":"The Opposite Effects of Kynurenic Acid and Different Kynurenic Acid Analogs on Tumor Necrosis Factor-\u03b1 (Tnf-\u03b1) Production and Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) Expression","volume":"10","author":"M\u00e1ndi","year":"2019","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-011-0763-x","article-title":"Kynurenic Acid: A Metabolite With Multiple Actions and Multiple Targets in Brain and Periphery","volume":"119","author":"Moroni","year":"2012","journal-title":"J Neural Transm"},{"key":"B45","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s10194-016-0654-5","article-title":"KYNA Analogue SZR72 Modifies CFA-induced Dural Inflammation- Regarding Expression of pERK1\/2 and IL-1\u03b2 in the Rat Trigeminal Ganglion","volume":"17","author":"Luk\u00e1cs","year":"2016","journal-title":"J\u00a0Headache Pain"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12710","article-title":"Activated Platelets Present High Mobility Group Box 1 to Neutrophils, Inducing Autophagy and Promoting the Extrusion of Neutrophil Extracellular Traps","volume":"12","author":"Maugeri","year":"2014","journal-title":"J Thromb Haemost"},{"key":"B47","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s40478-019-0747-x","article-title":"Neutrophil Extracellular Trap Induced by HMGB1 Exacerbates Damages in the Ischemic Brain","volume":"7","author":"Kim","year":"2019","journal-title":"Acta Neuropathol Commun"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-011-0605-2","article-title":"Different Inhibitory Effects of Kynurenic Acid and a Novel Kynurenic Acid Analogue on Tumour Necrosis Factor-\u03b1 (Tnf-\u03b1) Production by Mononuclear Cells, HMGB1 Production by Monocytes and HNP1-3 Secretion by Neutrophils","volume":"383","author":"Tiszlavicz","year":"2011","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2020.165664","article-title":"Mitochondrial Permeability Transition Pore is Involved in Oxidative Burst and NETosis of Human Neutrophils","volume":"1866","author":"Vorobjeva","year":"2020","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709217200","article-title":"Localization of PTP-1B, Shp-2, and Src Exclusively in Rat Brain Mitochondria and Functional Consequences","volume":"283","author":"Arachiche","year":"2008","journal-title":"J Biol Chem"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-1003-2","article-title":"Kynurenic Acid Restores Nrf2 Levels and Prevents Quinolinic Acid-Induced Toxicity in Rat Striatal Slices","volume":"55","author":"Ferreira","year":"2018","journal-title":"Mol Neurobiol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.cmet.2018.01.004","article-title":"Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation","volume":"27","author":"Agudelo","year":"2018","journal-title":"Cell Metab"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2018.06.004","article-title":"NMDA and GABA Receptor Presence in Rat Heart Mitochondria","volume":"291","author":"Nesterov","year":"2018","journal-title":"Chem Biol Interact"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s42399-020-00298-w","article-title":"Excessive Activation of NMDA Receptors in the Pathogenesis of Multiple Peripheral Organs Via Mitochondrial Dysfunction, Oxidative Stress, and Inflammation","volume":"2","author":"Ma","year":"2020","journal-title":"SN Compr Clin Med"},{"key":"B55","doi-asserted-by":"publisher","first-page":"17","DOI":"10.4137\/IJTR.S37973","article-title":"Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria","volume":"9","author":"Baran","year":"2016","journal-title":"Int J Tryptophan Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.5847\/wjem.j.1920-8642.2020.04.004","article-title":"Effects of Sepsis on Hippocampal Volume and Memory Function","volume":"11","author":"Yuan","year":"2020","journal-title":"World J Emerg Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.02.034","article-title":"Tetracyclines Disturb Mitochondrial Function Across Eukaryotic Models: A Call for Caution in Biomedical Research","volume":"10","author":"Moullan","year":"2015","journal-title":"Cell Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.717157\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T10:10:13Z","timestamp":1628763013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.717157\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,12]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2021.717157"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.717157","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,12]]},"article-number":"717157"}}