{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:20Z","timestamp":1787028440153,"version":"build-2736575974"},"reference-count":168,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["11003"],"award-info":[{"award-number":["11003"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hungarian Government grants","award":["OTKA-K112333 (J.B.)"],"award-info":[{"award-number":["OTKA-K112333 (J.B.)"]}]},{"name":"European Union and the European Social Fund","award":["GINOP-2.3.2-15-2016-00043 (IRONHEARTH)"],"award-info":[{"award-number":["GINOP-2.3.2-15-2016-00043 (IRONHEARTH)"]}]},{"name":"European Union and the European Social Fund","award":["EFOP-3.6.2-16-2017-00006 (LIVE LONGER)"],"award-info":[{"award-number":["EFOP-3.6.2-16-2017-00006 (LIVE LONGER)"]}]},{"name":"European Union and the European Social Fund","award":["EFOP-3.6.3-VEKOP-16-2017-00009"],"award-info":[{"award-number":["EFOP-3.6.3-VEKOP-16-2017-00009"]}]},{"name":"Thematic Excellence Programme of the Ministry for Innovation and Technology in Hungary within the framework of the Space Sciences thematic program of the University of Debrecen","award":["ED_18-1-2019-0028"],"award-info":[{"award-number":["ED_18-1-2019-0028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Over the past decades, substantial work has established that hemoglobin oxidation and heme release play a pivotal role in hemolytic\/hemorrhagic disorders. Recent reports have shown that oxidized hemoglobins, globin-derived peptides, and heme trigger diverse biological responses, such as toll-like receptor 4 activation with inflammatory response, reprogramming of cellular metabolism, differentiation, stress, and even death. Here, we discuss these cellular responses with particular focus on their mechanisms that are linked to the pathological consequences of hemorrhage and hemolysis. In recent years, endogenous gasotransmitters, such as carbon monoxide (CO) and hydrogen sulfide (H2S), have gained a lot of interest in connection with various human pathologies. Thus, many CO and H2S-releasing molecules have been developed and applied in various human disorders, including hemolytic and hemorrhagic diseases. Here, we discuss our current understanding of oxidized hemoglobin and heme-induced cell and tissue damage with particular focus on inflammation, cellular metabolism and differentiation, and endoplasmic reticulum stress in hemolytic\/hemorrhagic human diseases, and the potential beneficial role of CO and H2S in these pathologies. More detailed mechanistic insights into the complex pathology of hemolytic\/hemorrhagic diseases through heme oxygenase-1\/CO as well as H2S pathways would reveal new therapeutic approaches that can be exploited for clinical benefit.<\/jats:p>","DOI":"10.3390\/ijms22010047","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T08:38:43Z","timestamp":1608712723000},"page":"47","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutic Potential of Carbon Monoxide (CO) and Hydrogen Sulfide (H2S) in Hemolytic and Hemorrhagic Vascular Disorders\u2014Interaction between the Heme Oxygenase and H2S-Producing Systems"],"prefix":"10.3390","volume":"22","author":[{"given":"Tam\u00e1s","family":"G\u00e1ll","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7549-5691","authenticated-orcid":false,"given":"D\u00e1vid","family":"Peth\u0151","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Faculty of Medicine, University of Debrecen, K\u00e1lm\u00e1n Laki Doctoral School, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annam\u00e1ria","family":"Nagy","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Faculty of Medicine, University of Debrecen, K\u00e1lm\u00e1n Laki Doctoral School, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Balla","sequence":"additional","affiliation":[{"name":"HAS-UD Vascular Biology and Myocardial Pathophysiology Research Group, Hungarian Academy of Sciences, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7923-2645","authenticated-orcid":false,"given":"J\u00f3zsef","family":"Balla","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0021-9258(19)51157-7","article-title":"The conversion of hematin to bile pigment","volume":"184","author":"London","year":"1950","journal-title":"J. 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