The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis

{ 'indexed': {'date-parts': [[2023, 11, 1]], 'date-time': '2023-11-01T07:24:22Z', 'timestamp': 1698823462343}, 'reference-count': 252, 'publisher': 'MDPI AG', 'issue': '11', 'license': [ { 'start': { 'date-parts': [[2023, 10, 31]], 'date-time': '2023-10-31T00:00:00Z', 'timestamp': 1698710400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Zinc is a structural component of proteins, functions as a catalytic co-factor in DNA ' 'synthesis and transcription of hundreds of enzymes, and has a regulatory role in protein–DNA ' 'interactions of zinc-finger proteins. For many years, zinc has been acknowledged for its ' 'anti-oxidative and anti-inflammatory functions. Furthermore, zinc is a potent inhibitor of ' 'caspases-3, -7, and -8, modulating the caspase-controlled apoptosis and necroptosis. In ' 'recent years, the immunomodulatory role of zinc in sepsis and COVID-19 has been investigated. ' 'Both sepsis and COVID-19 are related to various regulated cell death (RCD) pathways, ' 'including apoptosis and necroptosis. Lack of zinc may have a negative effect on many immune ' 'functions, such as oxidative burst, cytokine production, chemotaxis, degranulation, ' 'phagocytosis, and RCD. While plasma zinc concentrations decline swiftly during both sepsis ' 'and COVID-19, this reduction is primarily attributed to a redistribution process associated ' 'with the inflammatory response. In this response, hepatic metallothionein production ' 'increases in reaction to cytokine release, which is linked to inflammation, and this protein ' 'effectively captures and stores zinc in the liver. Multiple regulatory mechanisms come into ' 'play, influencing the uptake of zinc, the binding of zinc to blood albumin and red blood ' 'cells, as well as the buffering and modulation of cytosolic zinc levels. Decreased zinc ' 'levels are associated with increasing severity of organ dysfunction, prolonged hospital stay ' 'and increased mortality in septic and COVID-19 patients. Results of recent studies focusing ' 'on these topics are summarized and discussed in this narrative review. Existing evidence ' 'currently does not support pharmacological zinc supplementation in patients with sepsis or ' 'COVID-19. Complementation and repletion should follow current guidelines for micronutrients ' 'in critically ill patients. Further research investigating the pharmacological mechanism of ' 'zinc in programmed cell death caused by invasive infections and its therapeutic potential in ' 'sepsis and COVID-19 could be worthwhile.</jats:p>', 'DOI': '10.3390/antiox12111942', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 10, 31]], 'date-time': '2023-10-31T16:44:03Z', 'timestamp': 1698770643000}, 'page': '1942', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in ' 'COVID-19 and Sepsis', 'prefix': '10.3390', 'volume': '12', 'author': [ { 'ORCID': 'http://orcid.org/0000-0003-0928-6183', 'authenticated-orcid': False, 'given': 'George', 'family': 'Briassoulis', 'sequence': 'first', 'affiliation': [ { 'name': 'Postgraduate Program “Emergency and Intensive Care in Children, ' 'Adolescents, and Young Adults”, School of Medicine, University ' 'of Crete, 71003 Heraklion, Greece'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9789-9002', 'authenticated-orcid': False, 'given': 'Panagiotis', 'family': 'Briassoulis', 'sequence': 'additional', 'affiliation': [ { 'name': 'Second Department of Anesthesiology, Attikon University ' 'Hospital, School of Medicine, National and Kapodistrian ' 'University of Athens, 12462 Athens, Greece'}]}, { 'ORCID': 'http://orcid.org/0000-0002-0936-368X', 'authenticated-orcid': False, 'given': 'Stavroula', 'family': 'Ilia', 'sequence': 'additional', 'affiliation': [ { 'name': 'Postgraduate Program “Emergency and Intensive Care in Children, ' 'Adolescents, and Young Adults”, School of Medicine, University ' 'of Crete, 71003 Heraklion, Greece'}, { 'name': 'Paediatric Intensive Care Unit, University Hospital, School of ' 'Medicine, University of Crete, 71110 Heraklion, Greece'}]}, { 'ORCID': 'http://orcid.org/0000-0001-7622-202X', 'authenticated-orcid': False, 'given': 'Marianna', 'family': 'Miliaraki', 'sequence': 'additional', 'affiliation': [ { 'name': 'Paediatric Intensive Care Unit, University Hospital, School of ' 'Medicine, University of Crete, 71110 Heraklion, Greece'}]}, { 'given': 'Efrossini', 'family': 'Briassouli', 'sequence': 'additional', 'affiliation': [ { 'name': 'Infectious Diseases Department “MAKKA”, First Department of ' 'Paediatrics, “Aghia Sophia” Children’s Hospital, School of ' 'Medicine, National and Kapodistrian University of Athens, 11527 ' 'Athens, Greece'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 10, 31]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '1552', 'DOI': '10.1007/s00134-020-06151-x', 'article-title': 'Incidence and Mortality of Hospital- and ICU-Treated Sepsis: Results ' 'from an Updated and Expanded Systematic Review and Meta-Analysis', 'volume': '46', 'author': 'Mellhammar', 'year': '2020', 'journal-title': 'Intensive Care Med.'}, { 'key': 'ref_2', '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_3', 'doi-asserted-by': 'crossref', 'first-page': '2042', 'DOI': '10.1097/CCM.0000000000005195', 'article-title': 'Coronavirus Disease 2019 as Cause of Viral Sepsis: A Systematic Review ' 'and Meta-Analysis', 'volume': '49', 'author': 'Karakike', 'year': '2021', 'journal-title': 'Crit. 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