We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×

Carbon monoxide and its donors – their implications for medicine

    Weronika Adach

    Department of General Biochemistry, Faculty of Biology & Environmental Protection, University of Lodz, Pomorska 141/3, 90–236 Lodz, Poland

    &
    Beata Olas

    *Author for correspondence: Tel.: +48 426 354 484; Fax: +48 426 354 484;

    E-mail Address: beata.olas@biol.uni.lodz.pl

    Department of General Biochemistry, Faculty of Biology & Environmental Protection, University of Lodz, Pomorska 141/3, 90–236 Lodz, Poland

    Published Online:https://doi.org/10.4155/fmc-2018-0215

    Inhalation of high concentrations of carbon monoxide (CO) is known to lead to serious systemic complications and neuronal disturbances. However, it has been found that not only is CO produced endogenously, but also that low concentrations can bestow beneficial effects which may be of interest in biology and medicine. As translocation of CO through the human organism is difficult, small molecules known as CO-releasing molecules (CORMs) deliver controlled amounts of CO to biological systems, and these are of great interest from a medical point of view. These actions may prevent vascular dysfunction, regulate blood pressure, inhibit blood platelet aggregation or have anti-inflammatory effects. This review summarizes the functions of various CO-releasing molecules in biology and medicine.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

    References

    • 1 Ryter SW, Choi AMK. Regulation of autophagy in oxygen – dependent cellular stress. Curr. Pharm. Des. 19, 2747–2756 (2013).
    • 2 Babu D, Motterlini R, Lefebvre RA. CO and CO-releasing molecules (CO-RMs) in acute gastrointestinal inflammation. Br. J. Pharmacol. 172, 1557–1573 (2015).
    • 3 Gandini C, Castoldi AF, Candura SM et al. Carbon monoxide cardiotoxicity. Clin. Toxicol. 39, 35–44 (2001).
    • 4 Lippi G, Rastelli G, Meschi T, Borghi L, Cervellin G. Pathophysiology, clinics, diagnosis and treatment of heart involvement in carbon monoxide poisoning. Clin. Biochem. 45, 1278–1285 (2012).
    • 5 Zapora E, Jarocka I. Hemoglobina – źródłem reaktywnych form tlenu. Postepy Hig. Med. Dosw. 67, 214–220 (2013).
    • 6 Jasnos K, Magierowski M, Kwiecień S, Brzozowski T. Tlenek węgla w fizjologii organizmu człowieka – rola w układzie pokarmowym. Postepy Hig. Med. Dosw. 68, 101–109 (2014).
    • 7 Olas B. Carbon monoxide is not always a poison gas for human organism: physiological and pharmacological features of CO. Chem. Biol. Interact. 222, 37–43 (2014).
    • 8 Schatzschneider U. Novel lead structures and activation mechanisms for CO-releasing molecules (CORMs). Br. J. Pharmacol. 172, 1638–1650 (2015).
    • 9 Cheng Y, Mitchell-Flack M, Wang A, Levy R. Carbon monoxide modulates cytochrome oxidase activity and oxidative stress in the developing murine brain during isoflurane exposure. Free Radic. Biol. Med. 86, 191–199 (2015). •• The work is particularly interesting because it describes the effect of carbon monoxide (CO) and chemical compounds (CO-releasing molecules [CORM]) on oxidative stress and selected parameters of hemostasis.
    • 10 Suner S, Jay G. Carbon monoxide has direct toxicity on the myocardium distinct from effects of hypoxia in an ex vivo rat heart model. AEM 15, 59–65 (2008).
    • 11 Beltowski J, Jamroz A, Borkowska E. Oksygenaza hemowa i tlenek węgla w fizjologii i patologii układu krążenia. Postepy Hig. Med. Dosw. 58, 83–99 (2004).
    • 12 Ufnal M, Żera T. Rola tlenku azotu, siarkowodoru oraz tlenku węgla w regulacji układu krążenia i ich potencjał farmakoterapeutyczny. Kardiol. Pol. 68, 436–440 (2010).
    • 13 Olas B. Gasomediators (·NO, CO, and H2S) and their role in hemostasis and thrombosis. Clin. Chim. Acta 445, 115–121 (2015).
    • 14 Nakao A. Therapeutic medical gas. In: Gas Biology Research in Clinical Practice. Yoshikawa T, Naito Y (Eds). Karger, Basel, 15–23 (2011).
    • 15 Feng W, Liu D, Zhai Q, Feng G. Lighting up carbon monoxide in living cells by a readily available and highly sensitive colorimetric and fluorescent probe. Anal. Chem. 240, 625–630 (2017).
    • 16 Nikolic I, Saksida T, Mangano K. Pharmacological application of carbon monoxide ameliorates islet-directed autoimmunity in mice via anti-inflammatory and anti-apoptotic effects. Diabetologia 5, 980–990 (2014).
    • 17 Santos-Silva T, Mukhopadhyay A, Seixas J, Bernardes G, Romăo C, Romăo M. Towards improved therapeutic CORMs: understanding the reactivity of CORM-3 with proteins. Curr. Med. Chem. 18, 3361–3366 (2011).
    • 18 Ji X, Damera K, Zheng Y, Yu B, Otterbein LE, Wang B. Toward carbon monoxidee based therapeutics: critical drug delivery and develop ability Issues. J. Pharm. Sci. 105, 406–416 (2016).
    • 19 McCoubrey WK Jr, Huang TJ, Maines MD. Heme oxygenase-2 is a hemoprotein and binds heme through heme regulatory motifs that are not involved in eme catalysis. J. Biol. Chem. 272, 12568–12574 (1997).
    • 20 Otterbein LE, Choi AMK. Heme oxygenase: colors of defense against cellular stress. Am. J. Physiol. Lung Cell. Mol. Physiol. 279, 1029–1037 (2000).
    • 21 Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH. Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nat. Cell Biol. 5, 1051–1061 (2003).
    • 22 Wu L, Wang R. Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol. Rev. 57, 585–630 (2005).
    • 23 Peers Ch, Steele DS. Carbon monoxide: a vital signalling molecule and potent toxin in the myocardium. J. Mol. Cell. Cardiol. 52, 359–365 (2012).
    • 24 Tadeusiewicz J, Olas B. Tlenek azotu i tlenek węgla – dwa ważne gazotransmitery. Kosmos 63, 543–554 (2014).
    • 25 Durante W, Johnson FK, Robert A, Johnson RA. Role of carbon monoxide in cardiovascular function. J. Cell. Mol. Med. 10, 672–686 (2006).
    • 26 Roamo C, Blattler W, Seixas J, Bernardes G. Developing drug molecules for therapy with carbon monoxide. Chem. Soc. Rev. 41, 3571–3583 (2012).
    • 27 Romanski S, Kraus B, Schatzschneider U, Neudorfl J, Amslinger S, Schmaltz H. Acyloxybutadiene iron tricarbonyl complexes as enzyme triggered CO-releasing molecules (ET-CORMs). Angew. Chem. Int. Ed. Engl. 50, 2392–2396 (2011).
    • 28 Agostinis P, Berg K, Cengel K, Foster T, Girotti A, Gollnick S et al. Photodynamic therapy of cancer: an update. CA Cancer J. Clin. 61, 250–281 (2011). • The mentioned article is particularly interesting because it draws attention to the anticancer properties of chemical compounds.
    • 29 Clark JE, Naughton P, Shurey S et al. Cardioprotective actions by a water-soluble carbon monoxide - releasing molecule. Circ. Res. 93, 2–8 (2003).
    • 30 Motterlini R, Mann BE, Foresti R. Therapeutic applications of carbon monoxide-releasing molecules. Expert Opin. Investig. Drugs 14, 1305–1318 (2005).
    • 31 Abeyrathna N, Washington K, Bashurb Ch, Liao Y. Nonmetallic carbon monoxide releasing molecules (CORMs). Org. Biomol. Chem. 15, 8692–8699 (2017).
    • 32 Slanina T, Šebej P. Visible-light activated photoCORMs: rational design of CO-releasing organic molecules absorbing in the tissue-transparent window. Photochem. Photobiol. Sci. 17, 692–710 (2018).
    • 33 Rodella L, Lamon BD, Rezzani R, Sangras B, Goodman AI, Falck JR, Abraham NG. Carbon monoxide and biliverdin prevent endothelial cell sloughing in rats with type I diabetes. Free Radic. Biol. Med. 40, 2198–2205 (2006).
    • 34 Winburn IC, Gunatunga1 K, McKernan RD, Walker RJ, Sammut IA, Harrison JC. Cell damage following carbon monoxide releasing molecule exposure: implications for therapeutic applications. Basic Clin. Pharmacol. Toxicol. 111, 31–41 (2012).
    • 35 Gupta N, Ragsdale SW. Thiol-disulfide redox dependence of heme binding and heme ligand witching in nuclear hormone receptor Rev-erbβ. J. Biol. Chem. 286, 4392–4403 (2011).
    • 36 Fujisaki N, Nakao A, Osako T et al. Can carbon monoxide-poisoned victims be organ donors. Med. Gas Res. 4, 1–4 (2014).
    • 37 Ozaki KS, Kimura S, Murase N. Use of carbon monoxide in minimizing ischemia/reperfusion injury in transplantation. Transplant. Rev. 26, 125–139 (2012).
    • 38 Motterlini R, Clark JE, Foresti R, Sarathchandra P, Mann BE, Green CJ. Carbon monoxide–releasing molecules characterization of biochemical and vascular activities. Circ. Res. 90, 17–24 (2002).
    • 39 Sun BW, Chen ZY, Chen X, Liu C. Attenuation of leukocytes sequestration by carbon monoxide-releasing molecules: liberated carbon monoxide in the liver of thermally injured mice. J. Burn Care Res. 28, 173–181 (2007).
    • 40 Magierowski M, Magierowska K, Hubalewska-Mazgaj M et al. Carbon monoxide released from its pharmacological donor, tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre-existing gastric ulcers. Br. J. Pharmacol. 174, 3654–3668 (2017).
    • 41 Ruan Y, Wang L, Zhao Y et al. Carbon monoxide potently prevents ischemia-induced high-mobility group box 1 translocation and release and protects against lethal renal ischemia–reperfusion injury. Kidney Int. 86, 525–537 (2014).
    • 42 Lin HH, Chen YH, Chiang MT, Huang PL, Chau LY. Activator protein-2α mediates carbon monoxide - induced stromal cell–derived factor-1α expression and vascularization in ischemic heart. Arterioscler. Thromb. Vasc. Biol. 33, 785–794 (2013).
    • 43 Sun B, Sun Z, Jin Q, Chen X. CO-releasing molecules (CORM-2)-liberated CO attenuates leukocytes infiltration in the renal tissue of thermally injured mice. Int. J. Biol. Sci. 4, 176–183 (2008).
    • 44 Soni H, Pandya G, Patel P, Acharya A, Jain M, Mehta A. Beneficial effects of carbon monoxide-releasing molecule-2 (CORM-2) on acute doxorubicin cardiotoxicity in mice: role of oxidative stress and apoptosis. Toxicol. Appl. Pharmacol. 253, 70–80 (2011). •• The work is particularly interesting because it describes the effect of CO and chemical compounds (CORM) on oxidative stress and selected parameters of hemostasis.
    • 45 Nielsen VG, Garza JI. Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human plasma. Blood Coagul. Fibrinol. 25, 801–805 (2014).
    • 46 Nielsen HG, Pretorius E. Iron and carbon monoxide enhance coagulation and attenuate fibrinolysis by different mechanisms. Blood Coagul. Fibrinol. 25, 695–702 (2014).
    • 47 Liu J, Fedinec AL, Leffler ChW, Parfenova H. Enteral supplements of a carbon monoxide donor CORM-A1 protect against cerebrovascular dysfunction caused by neonatal seizures. J. Cereb. Blood Flow Metab. 35, 193–199 (2015).
    • 48 Liu D, Wang X, Qin W et al. Suppressive effect of exogenous carbon monoxide on endotoxin-stimulated platelet over-activation via the glycoprotein-mediated PI3K-Akt-GSK3β pathway. Sci. Rep. 28, 110–116 (2016).
    • 49 Adach W, Olas B. The role of CORM-2 as a modulator of oxidative stress and hemostatic parameters of human plasma in vitro. PLoS ONE 12, 1–12 (2017). •• The work is particularly interesting because it describes the effect of CO and chemical compounds (CORM) on oxidative stress and selected parameters of hemostasis.
    • 50 Nielsen VG, Malayaman SN, Khan ES, Kirklin JK, George JF. Carbon monoxide releasing molecule-2 increases fibrinogen-dependent coagulation kinetics but does not enhance prothrombin activity. Blood Coagul. Fibrinol. 21, 349–353 (2010).
    • 51 Nielsen VG, Kirklin JK, George JF. Carbon monoxide releasing molecule-2 increases the velocity of thrombus growth and strength in human plasma. Blood Coagul. Fibrinol. 20, 377–380 (2009).
    • 52 Nielsen VG, Arkebauer MR, Wasko KA, Malayaman SN, Vosseller K. Carbon monoxide releasing molecule-2 decreases fibrinolysis in vitro and in vivo in the rabbit. TRAUMA 23, 104–107 (2011).
    • 53 Maruyama K, Morishita E, Yuno T et al. Carbon monoxide (CO)-releasing molecule-derived CO regulates tissue factor and plasminogen activator inhibitor type 1 in human endothelial cells. Thromb. Res. 130, 188–193 (2012). •• The work is particularly interesting because it describes the effect of CO and chemical compounds (CORM) on oxidative stress and selected parameters of hemostasis.
    • 54 Srisook K, Han S-S, Choi H-S et al. CO from enhanced HO activity or from CORM-2 inhibits both O2 and NO production and downregulates HO-1 expression in LPS-stimulated macrophages. Biochem. Pharmacol. 71, 307–318 (2006).
    • 55 Tsai MH, Lee ChW, Hsu LF. CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression. Redox Biol. 12, 377–388 (2017).
    • 56 Otterbein LE, Soares MP, Yamashita K, Bach FH. Heme oxygenase-1: unleashing the protective properties of heme. Trends Immunol. 24, 449–455 (2003).
    • 57 Chen H, Wang W, Xie H et al. A pathogenic role of IL- 17 at the early stage of corneal allograft rejection. Transplant. Immunol. 21, 155–161 (2009).
    • 58 Cepinskas G, Katada K, Bihari A, Potter RF. Carbon monoxide liberated from carbon monoxide-releasing molecule CORM-2 attenuates inflammation in the liver of septic mice. Am. J. Physiol. Gastrointest. Liver Physiol. 294, G184–G191 (2008).
    • 59 Steiger C, Luhmann T, Meinel L. Oral drug delivery of therapeutic gases – Carbon monoxide release for gastrointestinal diseases. J. Control Rel. 189, 46–53 (2014).
    • 60 Magierowski M, Magierowska K, Szmyd J et al. Hydrogen sulfide and carbon monoxide protect gastric mucosa compromised by mild stress against alendronate injury. Dig. Diseases Sci. 61, 3176–3189 (2016).
    • 61 Allanson M, Reeve VE. Carbon monoxide signalling reduces photocarcinogenesis in the hairless mouse. Cancer Immunol. Immunother. 56, 1807–1815 (2007). • The mentioned article is particularly interesting because it draws attention to the anticancer properties of chemical compounds.
    • 62 Shao L, Gu YY, Jiang CH, Liu CY, Lv LP, Liu JN, Zou Y. Carbon monoxide releasing molecule-2 suppresses proliferation, migration, invasion, and promotes apoptosis in non-small cell lung cancer Calu-3 cells. Eur. Rev. Med. Pharmacol. Sci. 22, 1948–1957 (2018).
    • 63 Nemecek D, Dvoráková M, Heroutová I, Chmelíková E, Sedmíková M. Anti-apoptotic properties of carbon monoxide in porcine oocyte during in vitro aging. Peer J. 3876, 1–25 (2017).
    • 64 Kramkowski K, Leszczynska A, Mogielnicki A et al. Antithrombotic properties of water-soluble carbon monoxide-releasing molecules. Arterioscler. Thromb. Vasc. Biol. 32, 2149–2157 (2012).
    • 65 Motterlini R, Mann BE, Johnson TR, Clark JE, Foresti R, Green CJ. Bioactivity and pharmacological actions of carbon monoxide-releasing molecules. Curr. Pharm. Des. 9, 2525–2539 (2003).
    • 66 Taylor MA. Effect of carbon monoxide-releasing molecule-3 on the severity of endothelial dysfunction due to elevation of hydrostatic pressure in an in vitro model of compartment syndrome. Electronic Thesis and Dissertation Repository 5007, 1–152 (2017).
    • 67 Foresti R, Hammad J, Clark JE et al. Vasoactive properties of CORM-3, a novel water-soluble carbon monoxide-releasing molecule. Br. J. Pharmacol. 142, 453–460 (2004).
    • 68 Sandouka A, Fuller BJ, Mann BE, Green CJ, Foresti R, Motterlini R. Treatment with CO-RMs during cold storage improves renal function at reperfusion. Kidney Int. 69, 239–247 (2006).
    • 69 Sener A, Tran K, Deng JP et al. Carbon monoxide releasing molecules inhibit cell death resulting from renal transplantation related stress. J. Urol. 190, 772–778 (2013).
    • 70 Mizuguchi S, Stephen J, Bihari R et al. CORM-3-derived CO modulates polymorphonuclear leukocyte migration across the vascular endothelium by reducing levels of cell surface-bound elastase. Am. J. Physiol. Heart Circ. Physiol. 297, H920–H929 (2009).
    • 71 Motterlini R, Sawle P, Bains S et al. CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule. FASEB J. 19, 284–286 (2004).
    • 72 Kretschmer R, Gessner G, Görls H, Heinemann SH, Westerhausen M. Dicarbonyl-bis(cysteamine)iron(II): A light induced carbon monoxide releasing molecule based on iron (CORM-S1). J. Inorg. Biochem. 105, 6–9 (2011).
    • 73 Gullotta F, Di Masi A, Ascenzi P. Carbon monoxide: an unusual drug. IUBMB Life 64, 378–386 (2012).
    • 74 Sawle P, Hammad J, Fairlamb IJS et al. Bioactive properties of iron-containing carbon monoxide-releasing molecules. J. Pharmacol. Exp. Ther. 318, 403–410 (2006).
    • 75 Desmard M, Foresti R, Morin D et al. Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules. Antioxid. Redox Sign. 16, 153–163 (2012).
    • 76 Desmard M, Davidge KS, Bouvet O et al. A carbon monoxide-releasing molecule (CORM-3) exerts bactericidal activity against Pseudomonas aeruginosa and improves survival in an animal model of bacteraemia. FASEB J. 23, 1023–1031 (2009)
    • 77 Fayad-Kobeissi S, Ratovonantenaina J, Dabir'e H et al. Vascular and angiogenic activities of CORM-401, an oxidant-sensitive CO-releasing molecule. Biochem. Pharmacol. 102, 64–77 (2016).
    • 78 Bhattacharjee R, Richard-Mohamed M, Sun Q et al. CORM-401 reduces ischemia reperfusion injury in an ex vivo renal porcine model of the donation after cardiac death. Transplantation 102, 1066–1074 (2018).
    • 79 Wareham LK, McLean S, Begg R et al. The broad-spectrum antimicrobial potential of [Mn(CO)4(S2CNMe(CH2CO2H))], a water-soluble CO-Releasing Molecule (CORM-401): intracellular accumulation, transcriptomic and statistical analyses, and membrane polarization. Antioxid. Redox Sign. 28, 1286–1308 (2017).
    • 80 Kaczara P, Motterlini R, Rosen G et al. Carbon monoxide released by CORM-401 uncouples mitochondrial respiration and inhibits glycolysis in endothelial cells: a role for mitoBKCa channels. BBA – Bioenergetics 1847, 1297–1309 (2015).
    • 81 Prieto L, Rossier J, Derszniak K et al. Modified biovectors for the tuneable activation of anti-platelet carbon monoxide release. Chem. Commun. 52, 1–6 (2017).
    • 82 Basuroy S, Leffler ChW, Parfenova H. CORM-A1 prevents blood-brain barrier dysfunction caused by ionotropic glutamate receptor-mediated endothelial oxidative stress and apoptosis. Am. J. Physiol. Cell Physiol. 304, C1105–C1115 (2013). •• The work is particularly interesting because it describes the effect of CO and chemical compounds (CORM) on oxidative stress and selected parameters of hemostasis.
    • 83 Wilson JL, Wareham LK, McLean S. CO-releasing molecules have non-heme targets in bacteria: transcriptomic, mathematical modelling and biochemical analyses of CORM-3 [Ru(CO)3Cl(glycinate)] actions on a heme-deficient mutant of Escherichia coli. Antioxid. Redox Sign. 23, 148–162 (2015).
    • 84 Southam MH, Smith TW, Lyon RL. A Thiol-reactive Ru(II) ion, not CO release, underlies the potent antimicrobial and cytotoxic properties of CO-releasing molecule-3. Red. Biol. 18, 114–123 (2018).
    • 85 Tinajero-Trejo M, Denby KJ, Sedelnikova SE, Hassoubah SA, Mann BE, Poole RK. Carbon Monoxide-Releasing Molecule-3 (CORM-3; Ru(CO) 3Cl(Glycinate)) as a tool to study the concerted effects of carbon monoxide and nitric oxide on bacterial flavohemoglobin Hmp: applications and pitfalls. J. Biol. Chem. 289, 29471–29482 (2014).
    • 86 Soni H, Jain M, Mehta AA. Investigation into the mechanism(s) of antithrombotic effects of carbon monoxide releasing molecule-3 (CORM-3). Thromb. Res. 127, 551–559 (2011).
    • 87 Bang CS, Demirel I, Kruse R, Persson K. Global gene expression profiling and antibiotic susceptibility after repeated exposure to the carbon monoxide-releasing molecule-2 (CORM-2) in multidrug-resistant ESBL-producing uropathogenic Escherichia coli. PLoS ONE 12, 1–25 (2016).
    • 88 Bang CS, Kruse R, Johansson K, Persson K. Carbon monoxide releasing molecule-2 (CORM-2) inhibits growth of multidrugresistant uropathogenic Escherichia coli in biofilm and following host cell colonization. BMC Microbiol. 64, 1–10 (2016).
    • 89 Inoue K, Patterson E, Capretta A, Lawendy A, Fraser D, Cepinskas G. Carbon monoxide releasing molecule-401 suppresses polymorphonuclear leukocyte migratory potential by modulating F-actin dynamics. Pathology 187, 1121–1133 (2017).