{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:29:53Z","timestamp":1792092593245,"version":"4.4.0"},"reference-count":235,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medicinal Research Reviews"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Carbon monoxide (CO) is an endogenous signaling molecule. It is produced via heme degradation by heme oxygenase (HMOX), releasing stoichiometric amounts of CO, iron, and biliverdin (then bilirubin). The HMOX\u2010CO axis has long been shown to offer beneficial effects by modulating inflammation, proliferation and cell death as they relate to tissue and organ protection. Recent years have seen a large number of studies examining CO pharmacology, its molecular targets, cellular mechanisms of action, pharmacokinetics, and detection methods using various delivery modalities including inhaled CO gas, CO solutions, and various types of CO donors. Unfortunately, one widely used donor type includes four commercially available carbonyl complexes with metal or borane, CORM\u20102 (Ru\n                    <jats:sup>2+<\/jats:sup>\n                    ), CORM\u20103 (Ru\n                    <jats:sup>2+<\/jats:sup>\n                    ), CORM\u2010A1 (BH\n                    <jats:sub>3<\/jats:sub>\n                    ), and CORM\u2010401 (Mn\n                    <jats:sup>+<\/jats:sup>\n                    ), which have been shown to have minimal and\/or unpredictable CO production and extensive CO\u2010independent chemical reactivity and biological activity. As a result, not all \u201cCO biological activities\u201d in the literature can be attributed to CO. In this review, we summarize key findings based on CO gas and CO in solution for the certainty of the active principal and to avoid data contamination resulting from the confirmed or potential reactivities and activities of the \u201ccarrier\u201d portion of CORMs. Along a similar line, we discuss interesting potential research areas of CO in the brain including a newly proposed CO\/HMOX\/dopamine axis and the role of CO in cognitive stimulation and circadian rhythm. This review is critical for the future development of the CO field by steering clear of complications caused by chemically reactive donor molecules.\n                  <\/jats:p>","DOI":"10.1002\/med.22116","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T03:55:16Z","timestamp":1745985316000},"page":"1275-1301","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Compelling Evidence: A Critical Update on the Therapeutic Potential of Carbon Monoxide"],"prefix":"10.1002","volume":"45","author":[{"given":"Nicola","family":"Bauer","sequence":"first","affiliation":[{"name":"Department of Chemistry and Center for Diagnostics and Therapeutics Georgia State University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyue","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Diagnostics and Therapeutics Georgia State University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1596-6315","authenticated-orcid":false,"given":"Aditi","family":"Vashistha","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Diagnostics and Therapeutics Georgia State University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupamaa","family":"Seshadri","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0917-0853","authenticated-orcid":false,"given":"Yi\u2010Chieh","family":"Nancy Du","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Weill Cornell Medicine New York City New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Otterbein","sequence":"additional","affiliation":[{"name":"Department of Surgery, Beth Israel Deaconess Medical Center Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-7699","authenticated-orcid":false,"given":"Chalet","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Tennessee Health Science Center Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark P.","family":"de Caestecker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2200-5270","authenticated-orcid":false,"given":"Binghe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Diagnostics and Therapeutics Georgia State University Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.03.003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14540"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","unstructured":"B.WangandL. 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