Rolle freier Radikale bei Lebererkrankungen

  • H. de Groot
  • U. Rauen
  • I. Ioannidis
  • J. Erhard
Conference paper

Zusammenfassung

Reaktive Sauerstoff- und Stickstoffspezies können direkt zytotoxisch und/oder als signalübertragende Moleküle wirken. Eine Beteiligung reaktiver Formen des Sauerstoffs an der Reperfusionsschädigung der Leber ist experimentell gesichert und erste Ergebnisse sprechen dafür, daß ihr auch bei der Reperfusionsschädigung der menschlichen Leber eine erhebliche Bedeutung zukommt. Bei Reperfusion der transplantierten Leber können reaktive Sauerstoffspezies von Hepatozyten, aktivierten Kupffer-Zellen und eingewanderten Neutrophilen freigesetzt werden. Die Bedingungen ihrer Freisetzung hängen von einer Vielzahl von Faktoren, u. a. der Dauer der ischämischen Phase und dem Ernährungszustand des Organs, ab. Granulozyten und Monozyten/Makrophagen sind auch die Zellen, die entscheidend zur Freisetzung reaktiver Sauerstoff- und Stickstoffspezies bei der Abstoßung eines Transplantats beitragen sollten.

Summary

Reactive oxygen and nitrogen species either mediate direct cell injury or act as signal-transmitting molecules. Participation of reactive oxygen species in reperfusion injury of the liver has been shown in several experimental systems and first results suggest that they may also play an important role in reperfusion injury of the human liver. Upon reperfusion of a transplanted liver reactive oxygen metabolites may be released by hepatocytes, activated Kupffer cells and invaded neutrophils. Conditions of their release may vary with several factors including the duration of the ischemic phase and the nutritional state of the organ. Neutrophils and monocytes/macrophages are those cells which should also decisively contribute to the release of reactive oxygen and nitrogen species upon rejection of a transplanted organ.

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Literatur

  1. 1.
    Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 87:1620–1624.PubMedCrossRefGoogle Scholar
  2. 2.
    Blumhardt G, Neuhaus P (1991) Does antioxidant treatment have a role in liver transplantation. Klin Wochenschr 69:1105–1108.PubMedCrossRefGoogle Scholar
  3. 3.
    Curzio M (1988) Interaction between neutrophils and 4-hydroxyalkenals and consequences on neutrophil motility. Free Rad Res Comms 5:55–66.CrossRefGoogle Scholar
  4. 4.
    Elstner EF (1990) Der Sauerstoff. Biochemie, Biologie, Medizin. Wissenschaftsverlag, Mannheim.Google Scholar
  5. 5.
    Galla H-J (1993) Stickstoffmonoxid, NO, ein interzellulärer Botenstoff. Angew Chemie 105:399–402.CrossRefGoogle Scholar
  6. 6.
    Groot H de (1992) Isolated cells in the study of the molecular mechanisms of reperfusion injury. Toxicol Lett 63:111–125.PubMedCrossRefGoogle Scholar
  7. 7.
    Groot H de (1994) Reactive oxygen species in tissue injury. Hepatogastroenterology 41:328–332.PubMedGoogle Scholar
  8. 8.
    Groot H de, Brecht M (1991) Reoxygenation injury in rat hepatocytes: Mediation by O2 /H2O2 liberated by sources other than xanthine oxidase. Biol Chem Hoppe-Seyler 372:35–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Groot H de, Anundi I, Littauer A (1989) Hypoxia-reoxygenation injury and the generation of reactive oxygen in isolated hepatocytes. Biomed Biochem 48:11–15.Google Scholar
  10. 10.
    Gyenes M, Groot H de (1993) Prostanoid release by Kupffer cells upon hypoxia-reoxygenation: role of pHi and Cai 2+. Am J Physiol 264:G535–G540.PubMedGoogle Scholar
  11. 11.
    Hibbs JBJ, Taintor RR, Vavrin Z, Rachlin EM (1988) Nitric oxide: A cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun 157:87–94.PubMedCrossRefGoogle Scholar
  12. 12.
    Hughes H, Farhood A, Jaeschke H (1992) Role of leukotriene B4 in the pathogenesis of hepatic ischemia-reperfusion injury in the rat. Prostagl Leukotr Essent Fatty Acids 45:113–119.CrossRefGoogle Scholar
  13. 13.
    Ioannidis I, Groot H de (1993) Cytotoxicity of nitric oxide in Fu5 rat hepatoma cells: evidence for co-operative action with hydrogen peroxide. Biochem J 296:341–345.PubMedGoogle Scholar
  14. 14.
    Ioannidis I, Hellinger A, Dehmlow C, Rauen U, Erhard J, Eigler FW, Groot H de (1995) Evidence for increased nitric oxide production after liver transplantation in humans. Transplantation 59:1293–1297.PubMedGoogle Scholar
  15. 15.
    Jaeschke H, Farhood A (1991) Neutrophil and Kupffer cell-induced oxidant stress and ischemia-reperfusion injury in rat liver. Am J Physiol 260:G355–G362.PubMedGoogle Scholar
  16. 16.
    Jaeschke H, Mitchell JR (1989) Mitochondria and xanthine oxidase both generate reactive oxygen species in isolated perfused rat liver after hypoxic injury. Biochem Biophys Res Commun 160:140–147.PubMedCrossRefGoogle Scholar
  17. 17.
    Jaeschke H, Farhood A, Bautista AP, Spolarics Z, Spitzer JJ (1993) Complement activates Kupffer cells and neutrophils during reperfusion after hepatic ischemia. Am J Physiol 264:G801–G809.PubMedGoogle Scholar
  18. 18.
    Kirkpatrick CH, Rqwlands DT (1992) Transplantation Immunology. JAMA 268:2952–2958.PubMedCrossRefGoogle Scholar
  19. 19.
    Kishimoto TK, Jutila MA, Berg EL, Butcher EC (1989) Neutrophil Mac-1 and MEL-14 adhesion proteins are inversely regulated by chemotactic factors. Science 245:1238–1241.PubMedCrossRefGoogle Scholar
  20. 20.
    Komatsu H, Koo A, Ghadishah E, Zeng H, Kuhlenkamp JF, Inoue M, Guth P, Kaplowitz N (1992) Neutrophil accumulation in ischemic perfused rat liver: evidence for a role for superoxide free radicals. Am J Physiol 262:G669–G676.PubMedGoogle Scholar
  21. 21.
    Langrehr JM, Hoffman RA, Lancaster JR, Simmons RL (1993) Nitric oxide — a new endogenous immunomodulator. Transplantation 55:1205–1212.PubMedCrossRefGoogle Scholar
  22. 22.
    Lewis MS, Whatley RE, Cain P, Mclntyre TM, Prescott SM, Zimmerman GA (1988) Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. J Clin Invest 82:2045–2055.PubMedCrossRefGoogle Scholar
  23. 23.
    Littauer A, Groot H de (1992) Release of reactive oxygen by hepatocytes on reoxygenation: three phases and role of mitochondria. Am J Physiol 262:G1015–G1020.PubMedGoogle Scholar
  24. 24.
    Mandel TE (1992) Basic immunology of transplantation. Med J Aust 157:126–131.PubMedGoogle Scholar
  25. 25.
    Marzi I, Knee J, Bühren V, Menger M, Trentz O (1992) Reduction by superoxide dismutase of leukocyte-endothelial adherence after liver transplantation. Surgery 111:90–97.PubMedGoogle Scholar
  26. 26.
    Mavier P, Preaux AM, Guigui B, Lescs MC, Zafrani ES, Dhumeaux D (1988) In vitro toxicity of polymorphonuclear neutrophils to rat hepatocytes: evidence for a proteinase-mediated mechanism. Hepatology 8:254–258.PubMedCrossRefGoogle Scholar
  27. 27.
    Nathan C (1992) Nitric oxide as a secretory product of mammalian cells. FASEB J 6:3051–3064.PubMedGoogle Scholar
  28. 28.
    Petrone WF, English DK, Wong K, McCord JM (1980) Free radicals and inflammation: Superoxide-dependent activation of a neutrophil chemotactic factor in plasma. Proc Natl Acad Sci USA 77:1159–1163.PubMedCrossRefGoogle Scholar
  29. 29.
    Rauen U, Viebahn R, Lauchart W, Groot H de (1994) The potential role of reactive oxygen species in liver ischemia/reperfusion injury following liver surgery. Hepatogastroenterology 41:333–336.PubMedGoogle Scholar
  30. 30.
    Rymsa B, Wang JF, Groot H de (1991) O2 -release by activated Kupffer cells upon hypoxia-reoxygenation. Am J Physiol 261:G602–G607.PubMedGoogle Scholar
  31. 31.
    Suzuki S, Toledo-Pereyra LH, Rodriguez FJ, Cejalvo D (1993) Neutrophil infiltration as an important factor in liver ischemia and reperfusion injury. Transplantation 55:1265–1272.PubMedCrossRefGoogle Scholar
  32. 32.
    Turner SR, Campbell JA, Lynn WS (1975) Polymorphonuclear leukocyte chemotaxis toward oxidized lipid components of cell membranes. J Exp Med 141:1437–1441.PubMedCrossRefGoogle Scholar
  33. 33.
    Weiss SJ (1989) Tissue destruction by neutrophils. N Engl J Med 320:365–376.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • H. de Groot
  • U. Rauen
  • I. Ioannidis
  • J. Erhard

There are no affiliations available

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