The Impact of Severe COVID-19 on Plasma Antioxidants
Neven Žarković, Anna Jastrząb, Iwona Jarocka-Karpowicz, Biserka Orehovec, Bruno Baršić, Marko Tarle, Marta Kmet, Ivica Lukšić, Wojciech Łuczaj, Elżbieta Skrzydlewska
Molecules, doi:10.3390/molecules27165323
Several studies suggested the association of COVID-19 with systemic oxidative stress, in particular with lipid peroxidation and vascular stress. Therefore, this study aimed to evaluate the antioxidant signaling in the plasma of eighty-eight patients upon admission to the Clinical Hospital Dubrava in Zagreb, of which twenty-two died within a week, while the other recovered. The differences between the deceased and the survivors were found, especially in the reduction of superoxide dismutases (SOD-1 and SOD-2) activity, which was accompanied by the alteration in glutathione-dependent system and the intensification of the thioredoxin-dependent system. Reduced levels of non-enzymatic antioxidants, especially tocopherol, were also observed, which correlated with enhanced lipid peroxidation (determined by 4-hydroxynonenal (4-HNE) and neuroprostane levels) and oxidative modifications of proteins assessed as 4-HNE-protein adducts and carbonyl groups. These findings confirm the onset of systemic oxidative stress in patients with severe SARS-CoV-2, especially those who died from COVID-19, as manifested by strongly reduced tocopherol level and SOD activity associated with lipid peroxidation. Therefore, we propose that preventive and/or supplementary use of antioxidants, especially of lipophilic nature, could be beneficial for the treatment of COVID-19 patients.
References
Amatore, Sgarbanti, Aquilano, Baldelli, Limongi et al., Influenza Virus Replication in Lung Epithelial Cells Depends on Redox-Sensitive Pathways Activated by NOX4-Derived ROS, Cell. Microbiol,
doi:10.1111/cmi.12343Anca, Toth, Kempler, Rizzo, Gender Differences in the Battle against COVID-19: Impact of Genetics, Comorbidities, Inflammation and Lifestyle on Differences in Outcomes, Int. J. Clin. Pract,
doi:10.1111/ijcp.13666Ayala, Muñoz, Argüelles, Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal, Oxidative Med. Cell. Longev,
doi:10.1155/2014/360438Bekyarova, Tzaneva, Bratoeva, Ivanova, Kotzev et al., 4-Hydroxynonenal (HNE) and Hepatic Injury Related to Chronic Oxidative Stress, Biotechnol. Biotechnol. Equip
Busnadiego, Kane, Rihn, Preugschas, Hughes et al., Host and Viral Determinants of Mx2 Antiretroviral Activity, J. Virol,
doi:10.1128/JVI.00214-14Chung, Zhang, Wooten, Borrelia Burgdorferi Elicited-IL-10 Suppresses the Production of Inflammatory Mediators, Phagocytosis, and Expression of Co-Stimulatory Receptors by Murine Macrophages and/or Dendritic Cells, PLoS ONE,
doi:10.1371/journal.pone.0084980Contoli, Papi, Tomassetti, Rizzo, Vieceli Dalla Sega et al., Blood Interferon-α Levels and Severity, Outcomes, and Inflammatory Profiles in Hospitalized COVID-19 Patients, Front. Immunol,
doi:10.3389/fimmu.2021.648004Coolen, Van Buuren, Duchateau, Upritchard, Verhagen, Kinetics of Biomarkers: Biological and Technical Validity of Isoprostanes in Plasma, Amino Acids,
doi:10.1007/s00726-005-0229-2Cuadrado, Rojo, Wells, Hayes, Cousin et al., Therapeutic Targeting of the NRF2 and KEAP1 Partnership in Chronic Diseases, Nat. Rev. Drug Discov,
doi:10.1038/s41573-018-0008-xDarenskaya, Kolesnikova, Kolesnikov, Free Radical Reactions in Socially Significant Infectious Diseases: HIV Infection, Hepatitis, Tuberculosis, Ann. Russ. Acad. Med. Sci,
doi:10.15690/vramn1328Derouiche, Oxidative Stress Associated with SARS-Cov-2 (COVID-19) Increases the Severity of the Lung Disease-A Systematic Review, J. Infect. Dis. Epidemiol,
doi:10.23937/2474-3658/1510121Dupuy, Le Faouder, Vigor, Oger, Galano et al., Simultaneous Quantitative Profiling of 20 Isoprostanoids from Omega-3 and Omega-6 Polyunsaturated Fatty Acids by LC-MS/MS in Various Biological Samples, Anal. Chim. Acta,
doi:10.1016/j.aca.2016.03.024Ebrahimi, Norouzi, Aazami, Moosavi-Movahedi, Review on Oxidative Stress Relation on COVID-19: Biomolecular and Bioanalytical Approach, Int. J. Biol. Macromol,
doi:10.1016/j.ijbiomac.2021.08.095Fernandes, De Brito, Dos Reis, Sato, Pereira, SARS-CoV-2 and Other Respiratory Viruses: What Does Oxidative Stress Have to Do with It?, Oxidative Med. Cell. Longev,
doi:10.1155/2020/8844280Fraternale, Zara, De Angelis, Nencioni, Palamara et al., Intracellular Redox-Modulated Pathways as Targets for Effective Approaches in the Treatment of Viral Infection, Int. J. Mol. Sci,
doi:10.3390/ijms22073603Ivanov, Bartosch, Isaguliants, Oxidative Stress in Infection and Consequent Disease, Oxidative Med. Cell. Longev,
doi:10.1155/2017/3496043Ivanović, Popović, Radulović, Medenica, Reversed-Phase Ion-Pair HPLC Determination of Some Water-Soluble Vitamins in Pharmaceuticals, J. Pharm. Biomed. Anal,
doi:10.1016/S0731-7085(98)00109-5Karkhanei, Talebi Ghane, Mehri, Evaluation of Oxidative Stress Level: Total Antioxidant Capacity, Total Oxidant Status and Glutathione Activity in Patients with COVID-19, New Microbes New Infect,
doi:10.1016/j.nmni.2021.100897Kelleher, Sha, Foster, Foster, Forrester et al., Thioredoxin-Mediated Denitrosylation Regulates Cytokine-Induced Nuclear Factor KB (NF-KB) Activation, J. Biol. Chem,
doi:10.1074/jbc.M113.503938Khomich, Kochetkov, Bartosch, Ivanov, Redox Biology of Respiratory Viral Infections, Viruses,
doi:10.3390/v10080392Komaravelli, Casola, Respiratory Viral Infections and Subversion of Cellular Antioxidant Defenses, J. Pharm. Pharm,
doi:10.4172/2153-0645.1000141Laforge, Elbim, Frère, Hémadi, Massaad et al., Tissue Damage from Neutrophil-Induced Oxidative Stress in COVID-19, Nat. Rev. Immunol,
doi:10.1038/s41577-020-0407-1Levine, Garland, Oliver, Amici, Climent et al., Determination of Carbonyl Content in Oxidatively Modified Proteins, Methods Enzymol,
doi:10.1016/0076-6879(90)86141-hLim, Leprivier, The Impact of Oncogenic RAS on Redox Balance and Implications for Cancer Development, Cell Death Dis,
doi:10.1038/s41419-019-2192-yLovell, Xie, Gabbita, Markesbery, Decreased Thioredoxin and Increased Thioredoxin Reductase Levels in Alzheimer's Disease Brain, Free Radic. Biol. Med,
doi:10.1016/S0891-5849(99)00258-0Maeso, García-Martínez, Rupérez, Cifuentes, Barbas, Capillary Electrophoresis of Glutathione to Monitor Oxidative Stress and Response to Antioxidant Treatments in an Animal Model, J. Chromatogr. B,
doi:10.1016/j.jchromb.2005.05.015Martín-Fernández, Aller, Heredia-Rodríguez, Gómez-Sánchez, Martínez-Paz et al., Lipid Peroxidation as a Hallmark of Severity in COVID-19 Patients, Redox Biol,
doi:10.1016/j.redox.2021.102181Miyazawa, Burdeos, Itaya, Nakagawa, Miyazawa et al., Regulatory Redox Interactions, IUBMB Life,
doi:10.1002/iub.2008Muhammad, Aminu, Ahmad, Iliya, Muhd et al., An Elevated 8-Isoprostaglandin F2 Alpha (8-Iso-PGF2α) in COVID-19 Subjects Co-Infected with Malaria, Pan. Afr. Med. J,
doi:10.11604/pamj.2020.37.78.25100Murata, Ohteki, Koyasu, Hamuro, IFN-Gamma and pro-Inflammatory Cytokine Production by Antigen-Presenting Cells Is Dictated by Intracellular Thiol Redox Status Regulated by Oxygen Tension, Eur. J. Immunol
Murata, Shimamura, Tagami, Takatsuki, Hamuro, The Skewing to Th1 Induced by Lentinan Is Directed through the Distinctive Cytokine Production by Macrophages with Elevated Intracellular Glutathione Content, Int. Immunopharmacol,
doi:10.1016/S1567-5769(01)00212-0Novaes, Teixeira, De Miranda, Oxidative Stress in Microbial Diseases: Pathogen, Host, and Therapeutics, Oxidative Med. Cell. Longev,
doi:10.1155/2019/8159562Paglia, Valentine, Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase, J. Lab Clin. Med
Pang, Zhou, Ewald, Chang, Hacariz et al., Using MetaboAnalyst 5.0 for LC-HRMS Spectra Processing, Multi-Omics Integration and Covariate Adjustment of Global Metabolomics Data, Nat. Protoc,
doi:10.1038/s41596-022-00710-wPincemail, Cavalier, Charlier, Cheramy-Bien, Brevers et al., Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study, Antioxidants,
doi:10.3390/antiox10020257Polonikov, Endogenous Deficiency of Glutathione as the Most Likely Cause of Serious Manifestations and Death in COVID-19 Patients, ACS Infect. Dis,
doi:10.1021/acsinfecdis.0c00288Schwartz, Conn, RNA Regulation of the Antiviral Protein 2 -5 -Oligoadenylate Synthetase, WIREs RNA,
doi:10.1002/wrna.1534Shastri, Shukla, Chong, Dua, Peterson et al., Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis, Oxidative Med. Cell. Longev,
doi:10.1155/2018/7695364Solis-Paredes, Montoya-Estrada, Cruz-Rico, Reyes-Muñoz, Perez-Duran et al., Plasma Total Antioxidant Capacity and Carbonylated Proteins Are Increased in Pregnant Women with Severe COVID-19, Viruses,
doi:10.3390/v14040723Spadaro, Fogagnolo, Campo, Zucchetti, Verri et al., Markers of Endothelial and Epithelial Pulmonary Injury in Mechanically Ventilated COVID-19 ICU Patients, Crit. Care,
doi:10.1186/s13054-021-03499-4Stoian, Banerjee, Rizvi, Rizzo, Diabetes and the COVID-19 Pandemic: How Insights from Recent Experience Might Guide Future Management, Metab. Syndr. Relat. Disord,
doi:10.1089/met.2020.0037Sykes, Mccormack, O'brien, A Preliminary Study of the Superoxide Dismutase Content of Some Human Tumors, Cancer Res
Trachootham, Lu, Ogasawara, Nilsa, Huang, Redox Regulation of Cell Survival, Antioxid. Redox Signal,
doi:10.1089/ars.2007.1957Tsikas, Rothmann, Schneider, Gutzki, Beckmann et al., Simultaneous GC-MS/MS Measurement of Malondialdehyde and 4-Hydroxy-2-Nonenal in Human Plasma: Effects of Long-Term L-Arginine Administration, Anal. Biochem,
doi:10.1016/j.ab.2016.08.009Van Den Brand, Haagmans, Van Riel, Osterhaus, Kuiken, The Pathology and Pathogenesis of Experimental Severe Acute Respiratory Syndrome and Influenza in Animal Models, J. Comp. Pathol,
doi:10.1016/j.jcpa.2014.01.004Vatassery, Brin, Fahn, Kayden, Traber, Effect of High Doses of Dietary Vitamin E on the Concentrations of Vitamin E in Several Brain Regions, Plasma, Liver, and Adipose Tissue of Rats, J. Neurochem,
doi:10.1111/j.1471-4159.1988.tb01083.xVieceli Dalla Sega, Fortini, Spadaro, Ronzoni, Zucchetti et al., Time Course of Endothelial Dysfunction Markers and Mortality in COVID-19 Patients: A Pilot Study, Clin. Transl. Med,
doi:10.1002/ctm2.283Völlmy, Van Den Toorn, Zenezini Chiozzi, Zucchetti, Papi et al., A Serum Proteome Signature to Predict Mortality in Severe COVID-19 Patients, Life Sci. Alliance,
doi:10.26508/lsa.202101099Weber, Milkovic, Bennett, Griffiths, Zarkovic et al., Measurement of HNE-Protein Adducts in Human Plasma and Serum by ELISA-Comparison of Two Primary Antibodies, Redox Biol,
doi:10.1016/j.redox.2013.01.012Wu, Wang, Zhang, Xu, Chen et al., Breaking the Vicious Loop between Inflammation, Oxidative Stress and Coagulation, a Novel Anti-Thrombus Insight of Nattokinase by Inhibiting LPS-Induced Inflammation and Oxidative Stress, Redox Biol,
doi:10.1016/j.redox.2020.101500Yaghoubi, Youssefi, Hashemy, Rafat Panah, Mashkani et al., Thioredoxin Reductase Gene Expression and Activity among Human T-Cell Lymphotropic Virus Type 1-Infected Patients, J. Med. Virol,
doi:10.1002/jmv.25371Ye, Zhang, Townsend, Tew, Oxidative Stress, Redox Regulation and Diseases of Cellular Differentiation, Biochim. Biophys. Acta Gen. Subj,
doi:10.1016/j.bbagen.2014.11.010Zarkovic, Jakovcevic, Mataic, Jaganjac, Vukovic et al., Post-Mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19, Cells
Zhou, Yu, Du, Fan, Liu et al., Clinical Course and Risk Factors for Mortality of Adult Inpatients with COVID-19 in Wuhan, China: A Retrospective Cohort Study, Lancet
Çakırca, Çakırca, Üstünel, Torun, Koyuncu et al., Thiol Level and Total Oxidant/Antioxidant Status in Patients with COVID-19 Infection, Ir. J. Med. Sci,
doi:10.1007/s11845-021-02743-8Žarković, Orehovec, Milković, Baršić, Tatzber et al., Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19, Antioxidants,
doi:10.3390/antiox10091341DOI record:
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"DOI": "10.1016/j.cotox.2017.11.002",
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"DOI": "10.1007/s12223-013-0239-5",
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"DOI": "10.1038/s41577-020-0407-1",
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"DOI": "10.1080/13102818.2019.1674690",
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"DOI": "10.1074/jbc.M113.503938",
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"DOI": "10.1038/s41573-018-0008-x",
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"DOI": "10.1002/jmv.25371",
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"DOI": "10.1371/journal.pone.0084980",
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"DOI": "10.1089/met.2020.0037",
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"article-title": "Studies on the Quantitative and Qualitative Characterization of Erythrocyte Glutathione Peroxidase",
"author": "Paglia",
"first-page": "158",
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"DOI": "10.1016/S0891-5849(99)00258-0",
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},
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"DOI": "10.1016/0076-6879(95)52023-6",
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"article-title": "A Preliminary Study of the Superoxide Dismutase Content of Some Human Tumors",
"author": "Sykes",
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"journal-title": "Cancer Res.",
"key": "ref64",
"volume": "38",
"year": "1978"
},
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"key": "ref65"
},
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"DOI": "10.1016/j.jchromb.2005.05.015",
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"DOI": "10.1111/j.1471-4159.1988.tb01083.x",
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},
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"DOI": "10.1016/j.ab.2016.08.009",
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},
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"DOI": "10.1007/s00726-005-0229-2",
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},
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"DOI": "10.1016/j.aca.2016.03.024",
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},
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"DOI": "10.1016/j.redox.2013.01.012",
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},
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},
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"DOI": "10.1038/s41596-022-00710-w",
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