{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T09:23:58Z","timestamp":1775035438938,"version":"3.50.1"},"reference-count":121,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T00:00:00Z","timestamp":1685491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Applied Molecular Biosciences Unit-UCIBIO","award":["UID\/Multi\/04378\/2019"],"award-info":[{"award-number":["UID\/Multi\/04378\/2019"]}]},{"name":"Applied Molecular Biosciences Unit-UCIBIO","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy","award":["UID\/Multi\/04378\/2019"],"award-info":[{"award-number":["UID\/Multi\/04378\/2019"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Carbon monoxide (CO) is a cytoprotective endogenous gas that is ubiquitously produced by the stress response enzyme heme-oxygenase. Being a gas, CO rapidly diffuses through tissues and binds to hemoglobin (Hb) increasing carboxyhemoglobin (COHb) levels. COHb can be formed in erythrocytes or in plasma from cell-free Hb. Herein, it is discussed as to whether endogenous COHb is an innocuous and inevitable metabolic waste product or not, and it is hypothesized that COHb has a biological role. In the present review, literature data are presented to support this hypothesis based on two main premises: (i) there is no direct correlation between COHb levels and CO toxicity, and (ii) COHb seems to have a direct cytoprotective and antioxidant role in erythrocytes and in hemorrhagic models in vivo. Moreover, CO is also an antioxidant by generating COHb, which protects against the pro-oxidant damaging effects of cell-free Hb. Up to now, COHb has been considered as a sink for both exogenous and endogenous CO generated during CO intoxication or heme metabolism, respectively. Hallmarking COHb as an important molecule with a biological (and eventually beneficial) role is a turning point in CO biology research, namely in CO intoxication and CO cytoprotection.<\/jats:p>","DOI":"10.3390\/antiox12061198","type":"journal-article","created":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T01:40:56Z","timestamp":1685583656000},"page":"1198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Carboxyhemoglobin (COHb): Unavoidable Bystander or Protective Player?"],"prefix":"10.3390","volume":"12","author":[{"given":"Andr\u00e9","family":"Carrola","sequence":"first","affiliation":[{"name":"UCIBIO, Applied Molecular Biosciences Unit, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]},{"given":"Carlos C.","family":"Rom\u00e3o","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9415-3742","authenticated-orcid":false,"given":"Helena L. A.","family":"Vieira","sequence":"additional","affiliation":[{"name":"UCIBIO, Applied Molecular Biosciences Unit, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"},{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.3181\/0706-MR-156","article-title":"The Human Red Blood Cell Proteome and Interactome","volume":"232","author":"Goodman","year":"2007","journal-title":"Exp. Biol. 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