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Kohlenmonoxid – Gift oder potenzielles Therapeutikum?

Carbon monoxide – poison or potential therapeutic?

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Zusammenfassung

Kohlenmonoxid (CO) ist weit mehr als nur ein toxisches Gas. Es wird endogen durch das Enzym Hämoxygenase synthetisiert und erfüllt essenzielle Funktionen unter physiologischen und pathophysiologischen Bedingungen. Untersuchungen der letzten Jahre attestieren CO antioxidative, antiinflammatorische, antiproliferative, antiapoptotische und vasodilatative Eigenschaften. Insbesondere bei anästhesiologisch und intensivmedizinisch relevanten Krankheitsbildern, wie dem „adult respiratory distress syndrome“ (ARDS), der Sepsis oder bei Organtransplantationen konnten in experimentellen Modellen zytoprotektive Wirkungen durch niedrig dosierte CO-Applikation nachgewiesen werden. Im Hinblick auf eine potenzielle therapeutische Anwendung beim Menschen werden in dieser Übersichtsarbeit funktionelle, protektive und toxische Wirkungen im Kontext des aktuellen Wissensstands kritisch diskutiert.

Abstract

Carbon monoxide (CO) is much more than just a toxic gas. Carbon monoxide is produced endogenously by the enzyme heme oxygenase and has important functions under physiological and pathophysiological conditions. Recent studies suggested antioxidative, anti-inflammatory, antiproliferative, anti-apoptotic, and vasodilating characteristics. Regarding clinically-relevant diseases in anesthesiology and critical care medicine, such as adult respiratory distress syndrome (ARDS), sepsis, or during organ transplantation, cytoprotective properties have been demonstrated by low-dose CO in experimental models. In view of a potential CO application in future human studies, this review discusses what is known to date about CO as it relates to functional, protective and toxic aspects.

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Literatur

  1. Akamatsu Y, Haga M, Tyagi S et al. (2004) Heme oxygenase-1-derived carbon monoxide protects hearts from transplant associated ischemia reperfusion injury. FASEB J 18: 771–772

    PubMed  Google Scholar 

  2. Ameredes BT, Otterbein LE, Kohut LK et al. (2003) Low-dose carbon monoxide reduces airway hyperresponsiveness in mice. Am J Physiol 285: L1270–1276

    Google Scholar 

  3. Amersi F, Shen XD, Anselmo D et al. (2002) Ex vivo exposure to carbon monoxide prevents hepatic ischemia/reperfusion injury through p38 MAP kinase pathway. Hepatology 35: 815–823

    Article  PubMed  Google Scholar 

  4. Amitai Y, Zlotogorski Z, Golan-Katzav V et al. (1998) Neuropsychological impairment from acute low-level exposure to carbon monoxide. Arch Neurol 55: 845–848

    Article  PubMed  Google Scholar 

  5. Antuni JD, Kharitonov SA, Hughes D et al. (2000) Increase in exhaled carbon monoxide during exacerbations of cystic fibrosis. Thorax 55: 138–142

    Article  PubMed  Google Scholar 

  6. Arguedas MR, Drake BB, Kapoor A, Fallon MB (2005) Carboxyhemoglobin levels in cirrhotic patients with and without hepatopulmonary syndrome. Gastroenterology 128: 328–333

    Article  PubMed  Google Scholar 

  7. Balla G, Jacob HS, Balla J et al. (1992) Ferritin: a cytoprotective antioxidant strategem of endothelium. J Biol Chem 267: 18148–18153

    PubMed  Google Scholar 

  8. Bel F van, Latour V, Vreman HJ et al. (2005) Is carbon monoxide-mediated cyclic guanosine monophosphate production responsible for low blood pressure in neonatal respiratory distress syndrome? J Appl Physiol 98: 1044–1049

    PubMed  Google Scholar 

  9. Berberat PO, Rahim YI, Yamashita K et al. (2005) Heme oxygenase-1-generated biliverdin ameliorates experimental murine colitis. Inflamm Bowel Dis 11: 350–359

    Article  PubMed  Google Scholar 

  10. Brouard S, Otterbein LE, Anrather J et al. (2000) Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis. J Exp Med 192: 1015–1026

    Article  PubMed  Google Scholar 

  11. Brouard S, Berberat PO, Tobiasch E et al. (2002) Heme oxygenase-1-derived carbon monoxide requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J Biol Chem 277: 17950–17961

    Article  PubMed  Google Scholar 

  12. Brune B, Ullrich V (1987) Inhibition of platelet aggregation by carbon monoxide is mediated by activation of guanylate cyclase. Mol Pharmacol 32: 497–504

    PubMed  Google Scholar 

  13. Burg R von (1999) Carbon monoxide. J Appl Toxicol 19: 379–386

    Article  PubMed  Google Scholar 

  14. Cardell LO, Lou YP, Takeyama K et al. (1998) Carbon monoxide, a cyclic GMP-related messenger, involved in hypoxic bronchodilation in vivo. Pulm Pharmacol Ther 11: 309–315

    Article  PubMed  Google Scholar 

  15. Carraway MS, Ghio AJ, Carter JD, Piantadosi CA (2000) Expression of heme oxygenase-1 in the lung in chronic hypoxia. Am J Physiol 278: L806–812

    Google Scholar 

  16. Chapman JT, Choi AM (2001) Exhaled monoxides as a pulmonary function test: use of exhaled nitric oxide and carbon monoxide. Clin Chest Med 22: 817–836

    Article  PubMed  Google Scholar 

  17. Chapman JT, Otterbein LE, Elias JA, Choi AM (2001) Carbon monoxide attenuates aeroallergen-induced inflammation in mice. Am J Physiol 281: L209–216

    Google Scholar 

  18. Chauveau C, Bouchet D, Roussel JC et al. (2002) Gene transfer of heme oxygenase-1 and carbon monoxide delivery inhibit chronic rejection. Am J Transplant 2: 581–592

    Article  PubMed  Google Scholar 

  19. Chen SM, Li YG, Wang DM (2005) Study on changes of heme oxygenase-1 expression in patients with coronary heart disease. Clin Cardiol 28: 197–201

    PubMed  Google Scholar 

  20. Chen YH, Chau LY, Lin MW et al. (2004) Heme oxygenase-1 gene promotor microsatellite polymorphism is associated with angiographic restenosis after coronary stenting. Eur Heart J 25: 39–47

    Article  PubMed  Google Scholar 

  21. Clayton CE, Carraway MS, Suliman HB et al. (2001) Inhaled carbon monoxide and hyperoxic lung injury in rats. Am J Physiol 281: L949–957

    Google Scholar 

  22. Coburn RF, Blakemore WS, Forster RE (1963) Endogenous carbon monoxide production in man. J Clin Invest 42: 1172–1178

    PubMed  Google Scholar 

  23. Coburn RF, Williams WJ, Kahn SB (1966) Endogenous carbon monoxide production in patients with hemolytic anemia. J Clin Invest 45: 460–468

    PubMed  Google Scholar 

  24. Coceani F (2000) Carbon monoxide in vasoregulation: the promise and the challenge. Circ Res 86: 1184–1186

    PubMed  Google Scholar 

  25. Deschamps D, Geraud C, Julien H et al. (2003) Memory one month after acute carbon monoxide intoxication: a prospective study. Occup Environ Med 60: 212–216

    Article  PubMed  Google Scholar 

  26. Dijkstra G, Blokzijl H, Bok L et al. (2004) Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of carbon monoxide. J Pathol 204: 296–303

    Article  PubMed  Google Scholar 

  27. Donnelly LE, Barnes PJ (2001) Expression of heme oxygenase in human airway epithelial cells. Am J Respir Cell Mol Biol 24: 295–303

    PubMed  Google Scholar 

  28. Dubuis E, Potier M, Wang R, Vandier C (2005) Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BKCa channels. Cardiovasc Res 65: 751–761

    Article  PubMed  Google Scholar 

  29. Eisenstein RS, Blemings KP (1998) Iron regulatory proteins, iron responsive elements and iron homeostasis. J Nutr 128: 2295–2298

    PubMed  Google Scholar 

  30. Farrugia G, Lei S, Lin X et al. (2003) A major role for carbon monoxide as an endogenous hyperpolarizing factor in the gastrointestinal tract. Proc Natl Acad Sci USA 100: 8567–8570

    Article  PubMed  Google Scholar 

  31. Fernandez M, Bonkovsky HL (1999) Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats. Hepatology 29: 1672–1679

    Article  PubMed  Google Scholar 

  32. Foresti R, Motterlini R (1999) The heme oxygenase pathway and its interaction with nitric oxide in the control of cellular homeostasis. Free Radic Res 31: 459–475

    PubMed  Google Scholar 

  33. Foresti R, Clark JE, Green CJ, Motterlini R (1997) Thiol compounds interact with nitric oxide in regulating heme oxygenase-1 induction in endothelial cells. Involvement of superoxide and peroxynitrite anions. J Biol Chem 272: 18411–18417

    Article  PubMed  Google Scholar 

  34. Foresti R, Hammad J, Clark JE et al. (2004) Vasoactive properties of CORM-3, a novel water-soluble carbon monoxide-releasing molecule. Br J Pharmacol 142: 453–460

    Article  PubMed  Google Scholar 

  35. Fujimoto H, Ohno M, Ayabe S et al. (2004) Carbon monoxide protects against cardiac ischemia-reperfusion injury in vivo via MAPK and Akt-eNOS pathways. Arterioscler Thromb Vasc Biol 24: 1848–1853

    Article  PubMed  Google Scholar 

  36. Fujita T, Toda K, Karimova A et al. (2001) Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis. Nat Med 7: 598–604

    Article  PubMed  Google Scholar 

  37. Ghosh S, Wilson MR, Choudhury S et al. (2005) Effects of inhaled carbon monoxide on acute lung injury in mice. Am J Physiol 288: L1003–1009

    Article  Google Scholar 

  38. Grosser N, Abate A, Oberle S et al. (2003) Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Biochem Biophys Res Commun 308: 956–960

    Article  PubMed  Google Scholar 

  39. Grover TR, Rairigh RL, Zenge JP et al. (2000) Inhaled carbon monoxide does not cause pulmonary vasodilation in the late-gestation fetal lamb. Am J Physiol 278: L779–784

    Google Scholar 

  40. Gunther L, Berberat PO, Haga M et al. (2002) Carbon monoxide protects pancreatic beta-cells from apoptosis and improves islet function/survival after transplantation. Diabetes 51: 994–999

    PubMed  Google Scholar 

  41. Hampson NB, Weaver LK, Piantadosi CA (2005) „Low-level“ carbon monoxide administration may carry risk. Am J Respir Crit Care Med 172: 784–785

    PubMed  Google Scholar 

  42. Hartsfield CL (2002) Cross talk between carbon monoxide and nitric oxide. Antioxid Redox Signal 4: 301–307

    Article  PubMed  Google Scholar 

  43. Hartsfield CL, Alam J, Cook JL, Choi AMK (1997) Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide. Am J Physiol 273: L980–988

    PubMed  Google Scholar 

  44. Hayashi M, Takahashi T, Morimatsu H et al. (2004) Increased carbon monoxide concentration in exhaled air after surgery and anesthesia. Anesth Analg 99: 444–448

    Article  PubMed  Google Scholar 

  45. Hegazi RA, Rao KN, Mayle A et al. (2005) Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. J Exp Med 202: 1703–1713

    Article  PubMed  Google Scholar 

  46. Hill-Kapturczak N, Chang SH, Agarwal A (2002) Heme oxygenase and the kidney. DNA Cell Biol 21: 307–321

    Article  PubMed  Google Scholar 

  47. Hoetzel A, Geiger K (2003) Stressproteine: Grundlagen und Bedeutung für die Anästhesie und Intensivmedizin. Anaesthesiol Intensivmed 44: 145–158

    Google Scholar 

  48. Hoetzel A, Vagts DA, Loop T et al. (2001) Effect of nitric oxide on shock-induced hepatic heme oxygenase-1 expression in the rat. Hepatology 33: 925–937

    Article  PubMed  Google Scholar 

  49. Hoetzel A, Geiger S, Loop T et al. (2002) Differential effects of volatile anesthetics on hepatic heme oxygenase-1 expression in the rat. Anesthesiology 97: 1318–1321

    Article  PubMed  Google Scholar 

  50. Hoetzel A, Leitz D, Schmidt R et al. (2006) Mechanism of hepatic heme oxygenase-1 induction by isoflurane. Anesthesiology 104: 101–109

    Article  PubMed  Google Scholar 

  51. Horvath I, Donnelly LE, Kiss A et al. (1998) Raised levels of exhaled carbon monoxide are associated with an increased expression of heme oxygenase-1 in airway macrophages in asthma: a new marker of oxidative stress. Thorax 53: 668–672

    PubMed  Google Scholar 

  52. Ignarro LJ, Buga GM, Wood KS et al. (1987) Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci U S A 84: 9265–9269

    Article  PubMed  Google Scholar 

  53. Kaizu T, Nakao A, Tsung A et al. (2005) Carbon monoxide inhalation ameliorates cold ischemia/reperfusion injury after rat liver transplantation. Surgery 138: 229–235

    Article  PubMed  Google Scholar 

  54. Ke B, Buelow R, Shen XD et al. (2002) Heme oxygenase 1 gene transfer prevents CD95/Fas ligand-mediated apoptosis and improves liver allograft survival via carbon monoxide signaling pathway. Hum Gene Ther 13: 1189–1199

    Article  PubMed  Google Scholar 

  55. Khatri SB, Ozkan M, McCarthy K et al. (2001) Alterations in exhaled gas profile during allergen-induced asthmatic response. Am J Respir Crit Care Med 164: 1844–1848

    PubMed  Google Scholar 

  56. Kim HP, Ryter SW, Choi AM (2006) CO as a cellular signaling molecule. Annu Rev Pharmacol Toxicol 46: 411–449

    Article  PubMed  Google Scholar 

  57. Kim YM, Bergonia HA, Muller C et al. (1995) Nitric oxide and intracellular heme. Adv Pharmacol 34: 277–291

    PubMed  Google Scholar 

  58. Kinhult J, Uddman R, Cardell LO (2001) The induction of carbon monoxide-mediated airway relaxation by PACAP 38 in isolated guinea pig airways. Lung 179: 1–8

    Article  PubMed  Google Scholar 

  59. Kirkby KA, Adin CA (2006) Products of heme oxygenase and their potential therapeutic applications. Am J Physiol 290: F563–571

    Google Scholar 

  60. Lavitrano M, Smolenski RT, Musumeci A et al. (2004) Carbon monoxide improves cardiac energetics and safeguards the heart during reperfusion after cardiopulmonary bypass in pigs. FASEB J 18: 1093–1095

    PubMed  Google Scholar 

  61. Lee PJ, Jiang BH, Chin BY et al. (1997) Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem 272: 5375–5381

    Article  PubMed  Google Scholar 

  62. Lee PJ, Camhi SL, Chin BY et al. (2000) AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1. Am J Physiol 279: L175–182

    Google Scholar 

  63. Lee TS, Chau LY (2002) Heme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice. Nat Med 8: 240–246

    Article  PubMed  Google Scholar 

  64. Li N, Venkatesan MI, Miguel A et al. (2000) Induction of heme oxygenase-1 expression in macrophages by diesel exhaust particle chemicals and quinones via the antioxidant-responsive element. J Immunol 165: 3393–3401

    PubMed  Google Scholar 

  65. Li P, Jiang H, Yang L et al. (2004) Angiotensin II induces carbon monoxide production in the perfused kidney: relationship to protein kinase C activation. Am J Physiol 287: F914–920

    Google Scholar 

  66. Lim S, Groneberg D, Fischer A et al. (2000) Expression of heme oxygenase isoenzymes 1 and 2 in normal and asthmatic airways: effect of inhaled corticosteroids. Am J Respir Crit Care Med 162: 1912–1918

    PubMed  Google Scholar 

  67. Liu XM, Chapman GB, Peyton KJ et al. (2002) Carbon monoxide inhibits apoptosis in vascular smooth muscle cells. Cardiovasc Res 55: 396–405

    Article  PubMed  Google Scholar 

  68. Maines MD, Trakshel GM, Kutty RK (1986) Characterization of two constitutive forms of rat liver microsomal heme oxygenase. Only one molecular species of the enzyme is inducible. J Biol Chem 261: 411–419

    PubMed  Google Scholar 

  69. Martins PN, Reuzel-Selke A, Jurisch A et al. (2005) Induction of carbon monoxide in the donor reduces graft immunogenicity and chronic graft deterioration. Transplant Proc 37: 379–381

    Article  PubMed  Google Scholar 

  70. Mayr FB, Spiel A, Leitner J et al. (2005) Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med 171: 354–360

    Article  PubMed  Google Scholar 

  71. Mazzola S, Forni M, Albertini M et al. (2004) Inhaled carbon monoxide (CO) prevents lung oedema induced by endotoxic shock. Vet Res Commun 28 [Suppl 1]: 209–212

  72. Mazzola S, Forni M, Albertini M et al. (2005) Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. FASEB J 19: 2045–2047

    PubMed  Google Scholar 

  73. McCoubrey WK Jr, Huang TJ, Maines MD (1997) Isolation and characterization of a cDNA from the rat brain that encodes hemoprotein heme oxygenase-3. Eur J Biochem 247: 725–732

    Article  PubMed  Google Scholar 

  74. McFaul SJ, McGrath JJ (1987) Studies on the mechanism of carbon monoxide-induced vasodilation in the isolated perfused rat heart. Toxicol Appl Pharmacol 87: 464–473

    Article  PubMed  Google Scholar 

  75. Mirza A, Eder V, Rochefort GY et al. (2005) CO inhalation at dose corresponding to tobacco smoke worsens cardiac remodeling after experimental myocardial infarction in rats. Toxicol Sci 85: 976–982

    Article  PubMed  Google Scholar 

  76. Moore BA, Otterbein LE, Turler A et al. (2003) Inhaled carbon monoxide suppresses the development of postoperative ileus in the murine small intestine. Gastroenterology 124: 377–391

    Article  PubMed  Google Scholar 

  77. Moore BA, Overhaus M, Whitcomb J et al. (2005) Brief inhalation of low-dose carbon monoxide protects rodents and swine from postoperative ileus. Crit Care Med 33: 1317–1326

    Article  PubMed  Google Scholar 

  78. Morisaki H, Katayama T, Kotake Y et al. (2002) Carbon monoxide modulates endotoxin-induced microvascular leukocyte adhesion through platelet-dependent mechanisms. Anesthesiology 97: 701–709

    Article  PubMed  Google Scholar 

  79. Morita T, Kourembanas S (1995) Endothelial cell expression of vasoconstrictors and growth factors is regulated by smooth muscle cell-derived carbon monoxide. J Clin Invest 96: 2676–2682

    PubMed  Google Scholar 

  80. Morita T, Perrella MA, Lee ME, Kourembanas S (1995) Smooth muscle cell-derived carbon monoxide is a regulator of vascular cGMP. Proc Natl Acad Sci USA 92: 1475–1479

    Article  PubMed  Google Scholar 

  81. Morita T, Mitsialis SA, Koike H et al. (1997) Carbon monoxide controls the proliferation of hypoxic vascular smooth muscle cells. J Biol Chem 272: 32804–32809

    Article  PubMed  Google Scholar 

  82. Morse D, Choi AM (2005) Heme oxygenase-1: from bench to bedside. Am J Respir Crit Care Med 172: 660–670

    Article  PubMed  Google Scholar 

  83. Morse D, Pischke SE, Zhou Z et al. (2003) Suppression of inflammatory cytokine production by carbon monoxide involves the JNK pathway and AP-1. J Biol Chem 278: 36993–36998

    Article  PubMed  Google Scholar 

  84. Motterlini R, Mann BE, Johnson TR et al. (2003) Bioactivity and pharmacological actions of carbon monoxide-releasing molecules. Curr Pharm Des 9: 2525–2539

    Article  PubMed  Google Scholar 

  85. Motterlini R, Mann BE, Foresti R et al. (2005) Therapeutic applications of carbon monoxide-releasing molecules. Expert Opin Investig Drugs 14: 1305–1318

    Article  PubMed  Google Scholar 

  86. Motterlini R, Sawle P, Hammad J et al. (2005) CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule. FASEB J 19: 284–286

    PubMed  Google Scholar 

  87. Nachar RA, Pastene CM, Herrera EA et al. (2001) Low-dose inhaled carbon monoxide reduces pulmonary vascular resistance during acute hypoxemia in adult sheep. High Alt Med Biol 2: 377–385

    Article  PubMed  Google Scholar 

  88. Naik JS, Walker BR (2003) Heme oxygenase-mediated vasodilation involves vascular smooth muscle cell hyperpolarization. Am J Physiol 285: H220–228

    Google Scholar 

  89. Nakao A, Kimizuka K, Stolz DB et al. (2003) Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury. Am J Pathol 163: 1587–1598

    PubMed  Google Scholar 

  90. Nakao A, Kimizuka K, Stolz DB et al. (2003) Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts. Surgery 134: 285–292

    Article  PubMed  Google Scholar 

  91. Nakao A, Moore BA, Murase N et al. (2003) Immunomodulatory effects of inhaled carbon monoxide on rat syngeneic small bowel graft motility. Gut 52: 1278–1285

    Article  PubMed  Google Scholar 

  92. Nakao A, Neto JS, Kanno S et al. (2005) Protection against ischemia/reperfusion injury in cardiac and renal transplantation with carbon monoxide, biliverdin and both. Am J Transplant 5: 282–291

    Article  PubMed  Google Scholar 

  93. Neto JS, Nakao A, Kimizuka K et al. (2004) Protection of transplant-induced renal ischemia-reperfusion injury with carbon monoxide. Am J Physiol 287: F979–989

    Article  PubMed  Google Scholar 

  94. Ning W, Choi AM, Li C (2005) Carbon monoxide inhibits IL-17-induced IL-6 production through the MAPK pathway in human pulmonary epithelial cells. Am J Physiol 289: L268–273

    Google Scholar 

  95. Ott MC, Scott JR, Bihari A et al. (2005) Inhalation of carbon monoxide prevents liver injury and inflammation following hind limb ischemia/reperfusion. FASEB J 19: 106–108

    PubMed  Google Scholar 

  96. Otterbein LE, Choi AM (2000) Heme oxygenase: colors of defense against cellular stress. Am J Physiol 279: L1029–1037

    PubMed  Google Scholar 

  97. Otterbein LE, Kolls JK, Mantell LL et al. (1999) Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J Clin Invest 103: 1047–1054

    PubMed  Google Scholar 

  98. Otterbein LE, Mantell LL, Choi AM (1999) Carbon monoxide provides protection against hyperoxic lung injury. Am J Physiol 276: L688–694

    PubMed  Google Scholar 

  99. Otterbein LE, Bach FH, Alam J et al. (2000) Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 6: 422–428

    Article  PubMed  Google Scholar 

  100. Otterbein LE, Otterbein SL, Ifedigbo E et al. (2003) MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury. Am J Pathol 163: 2555–2563

    PubMed  Google Scholar 

  101. Otterbein LE, Zuckerbraun BS, Haga M et al. (2003) Carbon monoxide suppresses arteriosclerotic lesions associated with chronic graft rejection and with balloon injury. Nat Med 9: 183–190

    Article  PubMed  Google Scholar 

  102. Pae HO, Oh GS, Choi BM et al. (2004) Carbon monoxide produced by heme oxygenase-1 suppresses T cell proliferation via inhibition of IL-2 production. J Immunol 172: 4744–4751

    PubMed  Google Scholar 

  103. Palmer RM, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526

    PubMed  Google Scholar 

  104. Pannen BHJ, Bauer M (1998) Differential regulation of hepatic arterial and portal venous vascular resistance by nitric oxide and carbon monoxide in rats. Life Sci 62: 2025–2033

    Article  PubMed  Google Scholar 

  105. Pannen BHJ, Köhler N, Hole B et al. (1998) Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats. J Clin Invest 102: 1220–1228

    PubMed  Google Scholar 

  106. Paredi P, Leckie MJ, Horvath I et al. (1999) Changes in exhaled carbon monoxide and nitric oxide levels following allergen challenge in patients with asthma. Eur Respir J 13: 48–52

    Article  PubMed  Google Scholar 

  107. Peterson JE, Stewart RD (1975) Predicting the carboxyhemoglobin levels resulting from carbon monoxide exposures. J Appl Physiol 39: 633–638

    PubMed  Google Scholar 

  108. Polte T, Abate A, Dennery PA, Schroder H (2000) Heme oxygenase-1 is a cGMP-inducible endothelial protein and mediates the cytoprotective action of nitric oxide. Arterioscler Thromb Vasc Biol 20: 1209–1215

    PubMed  Google Scholar 

  109. Raju VS, Imai N, Liang CS (1999) Chamber-specific regulation of heme oxygenase-1 (heat shock protein 32) in right-sided congestive heart failure. J Mol Cell Cardiol 31: 1581–1589

    Article  PubMed  Google Scholar 

  110. Ramos KS, Lin H, McGrath JJ (1989) Modulation of cyclic guanosine monophosphate levels in cultured aortic smooth muscle cells by carbon monoxide. Biochem Pharmacol 38: 1368–1370

    Article  PubMed  Google Scholar 

  111. Reade MC, Millo JL, Young JD, Boyd CA (2005) Nitric oxide synthase is downregulated, while haem oxygenase is increased, in patients with septic shock. Br J Anaesth 94: 468–473

    Article  PubMed  Google Scholar 

  112. Ryter SW, Alam J, Choi AM (2006) Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiol Rev 86: 583–650

    Article  PubMed  Google Scholar 

  113. Sarady JK, Otterbein SL, Liu F et al. (2002) Carbon monoxide modulates endotoxin-induced production of granulocyte macrophage colony-stimulating factor in macrophages. Am J Respir Cell Mol Biol 27: 739–745

    PubMed  Google Scholar 

  114. Sarady JK, Zuckerbraun BS, Bilban M et al. (2004) Carbon monoxide protection against endotoxic shock involves reciprocal effects on iNOS in the lung and liver. FASEB J 18: 854–856

    PubMed  Google Scholar 

  115. Sass G, Soares MC, Yamashita K et al. (2003) Heme oxygenase-1 and its reaction product, carbon monoxide, prevent inflammation-related apoptotic liver damage in mice. Hepatology 38: 909–918

    Article  PubMed  Google Scholar 

  116. Sass G, Seyfried S, Parreira SM et al. (2004) Cooperative effect of biliverdin and carbon monoxide on survival of mice in immune-mediated liver injury. Hepatology 40: 1128–1135

    Article  PubMed  Google Scholar 

  117. Sato K, Balla J, Otterbein L et al. (2001) Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. J Immunol 166: 4185–4194

    PubMed  Google Scholar 

  118. Schmidt R, Hoetzel A, Baechle T et al. (2004) Isoflurane pretreatment lowers portal venous resistance by increasing hepatic heme oxygenase activity in the rat liver in vivo. J Hepatol 41: 706–713

    Article  PubMed  Google Scholar 

  119. Sethi JM, Otterbein LE, Choi AM (2002) Differential modulation by exogenous carbon monoxide of TNF-alpha stimulated mitogen-activated protein kinases in rat pulmonary artery endothelial cells. Antioxid Redox Signal 4: 241–248

    Article  PubMed  Google Scholar 

  120. Shi Y, Pan F, Li H et al. (2003) Carbon monoxide concentrations in paediatric sepsis syndrome. Arch Dis Child 88: 889–990

    Article  PubMed  Google Scholar 

  121. Sikorski EM, Hock T, Hill-Kapturczak N, Agarwal A (2004) The story so far: molecular regulation of the heme oxygenase-1 gene in renal injury. Am J Physiol 286: F425–441

    Google Scholar 

  122. Sjostrand T (1951) Endogenous formation of carbon monoxide; the CO concentration in the inspired and expired air of hospital patients. Acta Physiol Scand 22: 137–141

    PubMed  Google Scholar 

  123. Slikker W Jr, Andersen ME, Bogdanffy MS et al. (2004) Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol Appl Pharmacol 201: 226–294

    Article  PubMed  Google Scholar 

  124. Soares MP, Seldon MP, Gregoire IP et al. (2004) Heme oxygenase-1 modulates the expression of adhesion molecules associated with endothelial cell activation. J Immunol 172: 3553–3563

    PubMed  Google Scholar 

  125. Song R, Mahidhara RS, Liu F et al. (2002) Carbon monoxide inhibits human airway smooth muscle cell proliferation via mitogen-activated protein kinase pathway. Am J Respir Cell Mol Biol 27: 603–610

    PubMed  Google Scholar 

  126. Song R, Kubo M, Morse D et al. (2003) Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects. Am J Pathol 163: 231–242

    PubMed  Google Scholar 

  127. Stanford SJ, Walters MJ, Mitchell JA (2004) Carbon monoxide inhibits endothelin-1 release by human pulmonary artery smooth muscle cells. Eur J Pharmacol 486: 349–352

    Article  PubMed  Google Scholar 

  128. Stein AB, Guo Y, Tan W et al. (2005) Administration of a CO-releasing molecule induces late preconditioning against myocardial infarction. J Mol Cell Cardiol 38: 127–134

    Article  PubMed  Google Scholar 

  129. Stockard-Sullivan JE, Korsak RA, Webber DS, Edmond J (2003) Mild carbon monoxide exposure and auditory function in the developing rat. J Neurosci Res 74: 644–654

    Article  PubMed  Google Scholar 

  130. Stocker R, Yamamoto Y, McDonagh AF et al. (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235: 1043–1046

    PubMed  Google Scholar 

  131. Stupfel M, Bouley G (1970) Physiological and biochemical effects on rats and mice exposed to small concentrations of carbon monoxide for long periods. Ann N Y Acad Sci 174: 342–368

    PubMed  Google Scholar 

  132. Suematsu M, Goda N, Sano T et al. (1995) Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest 96: 2431–2437

    PubMed  Google Scholar 

  133. Takahashi T, Morita K, Akagi R, Sassa S (2004) Protective role of heme oxygenase-1 in renal ischemia. Antioxid Redox Signal 6: 867–877

    PubMed  Google Scholar 

  134. Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc Natl Acad Sci USA 61: 748–755

    Article  PubMed  Google Scholar 

  135. Thom SR, Fisher D, Xu YA et al. (1999) Role of nitric oxide-derived oxidants in vascular injury from carbon monoxide in the rat. Am J Physiol 276: H984–992

    PubMed  Google Scholar 

  136. Thom SR, Weaver LK, Hampson NB (2005) „Therapeutic“ carbon monoxide may be toxic. Am J Respir Crit Care Med 171: 1318

    Google Scholar 

  137. Thorup C, Jones CL, Gross SS et al. (1999) Carbon monoxide induces vasodilation and nitric oxide release but suppresses endothelial NOS. Am J Physiol 277: F882–889

    PubMed  Google Scholar 

  138. Togane Y, Morita T, Suematsu M et al. (2000) Protective roles of endogenous carbon monoxide in neointimal development elicited by arterial injury. Am J Physiol 278: H623–632

    Google Scholar 

  139. Uasuf CG, Jatakanon A, James A et al. (1999) Exhaled carbon monoxide in childhood asthma. J Pediatr 135: 569–574

    Article  PubMed  Google Scholar 

  140. Vassalli F, Pierre S, Julien V et al. (2001) Inhibition of hypoxic pulmonary vasoconstriction by carbon monoxide in dogs. Crit Care Med 29: 359–366

    Article  PubMed  Google Scholar 

  141. Vedernikov YP, Graser T, Vanin AF (1989) Similar endothelium-independent arterial relaxation by carbon monoxide and nitric oxide. Biomed Biochim Acta 48: 601–603

    PubMed  Google Scholar 

  142. Vera T, Henegar JR, Drummond HA et al. (2005) Protective effect of carbon monoxide-releasing compounds in ischemia-induced acute renal failure. J Am Soc Nephrol 16: 950–958

    Article  PubMed  Google Scholar 

  143. Vreman HJ, Wong RJ, Stevenson DK (2000) Carbon monoxide in breath, blood, and other tissues. In: Penney DG (ed) Carbon monoxide poisoning. CRC Press LLC, Boca Raton, pp 19–60

  144. Wakabayashi Y, Takamiya R, Mizuki A et al. (1999) Carbon monoxide overproduced by heme oxygenase-1 causes a reduction of vascular resistance in perfused rat liver. Am J Physiol 277: G1088–1096

    PubMed  Google Scholar 

  145. Wang H, Lee SS, Gao W et al. (2005) Donor treatment with carbon monoxide can yield islet allograft survival and tolerance. Diabetes 54: 1400–1406

    PubMed  Google Scholar 

  146. Winestone JS, Bonner C, Leffler CW (2003) Carbon monoxide as an attenuator of vasoconstriction in piglet cerebral arterioles. Exp Biol Med 228: 46–50

    Google Scholar 

  147. Wolff DG (1976) The formation of carbon monoxide during peroxidation of microsomal lipids. Biochem Biophys Res Commun 73: 850–857

    Article  PubMed  Google Scholar 

  148. Wu L, Wang R (2005) Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev 57: 585–630

    Article  PubMed  Google Scholar 

  149. Yachie A, Niida Y, Wada T et al. (1999) Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 103: 129–135

    PubMed  Google Scholar 

  150. Yamaya M, Sekizawa K, Ishizuka S et al. (1999) Exhaled carbon monoxide levels during treatment of acute asthma. Eur Respir J 13: 757–760

    Article  PubMed  Google Scholar 

  151. Yasuda H, Yamaya M, Nakayama K et al. (2005) Increased arterial carboxyhemoglobin concentrations in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 171: 1246–1251

    Article  PubMed  Google Scholar 

  152. Zanconato S, Scollo M, Zaramella C et al. (2002) Exhaled carbon monoxide levels after a course of oral prednisone in children with asthma exacerbation. J Allergy Clin Immunol 109: 440–445

    Article  PubMed  Google Scholar 

  153. Zegdi R, Perrin D, Burdin M et al. (2002) Increased endogenous carbon monoxide production in severe sepsis. Intensive Care Med 28: 793–796

    Article  PubMed  Google Scholar 

  154. Zhang X, Shan P, Alam J et al. (2003) Carbon monoxide modulates Fas/Fas ligand, caspases, and Bcl-2 family proteins via the p38alpha mitogen-activated protein kinase pathway during ischemia-reperfusion lung injury. J Biol Chem 278: 22061–22070

    Article  PubMed  Google Scholar 

  155. Zhang X, Shan P, Otterbein LE et al. (2003) Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J Biol Chem 278: 1248–1258

    Article  PubMed  Google Scholar 

  156. Zhou Z, Song R, Fattman CL et al. (2005) Carbon monoxide suppresses bleomycin-induced lung fibrosis. Am J Pathol 166: 27–37

    PubMed  Google Scholar 

  157. Zuckerbraun BS, Billiar TR, Otterbein SL et al. (2003) Carbon monoxide protects against liver failure through nitric oxide-induced heme oxygenase 1. J Exp Med 198: 1707–1716

    Article  PubMed  Google Scholar 

  158. Zuckerbraun BS, McCloskey CA, Gallo D et al. (2005) Carbon monoxide prevents multiple organ injury in a model of hemorrhagic shock and resuscitation. Shock 23: 527–532

    PubMed  Google Scholar 

  159. Zuckerbraun BS, Otterbein LE, Boyle P et al. (2005) Carbon monoxide protects against the development of experimental necrotizing enterocolitis. Am J Physiol 289: G607–613

    Google Scholar 

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  1. Dep. of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh Medical Center, W640 Montefiore University Hospital, 3459 Fifth Avenue, Pittsburgh PA 15213, USA

    A. Hoetzel

  2. Anaesthesiologische Universitätsklinik, Freiburg, Deutschland

    A. Hoetzel & R. Schmidt

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Hoetzel, A., Schmidt, R. Kohlenmonoxid – Gift oder potenzielles Therapeutikum?. Anaesthesist 55, 1068–1079 (2006). https://doi.org/10.1007/s00101-006-1056-x

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