Freie Sauerstoffradikale: Biologische Grundlagen und Nachweismethoden

  • M. Saran
Conference paper

Zusammenfassung

Die mit chemischen und strahlenchemischen Methoden in vitro erarbeiteten Kenntnisse über Radikalreaktionen sind nur mit großen Einschränkungen auf die Verhältnisse in vivo übertragbar. Gesetzmäßigkeiten der chemischen Kinetik lassen sich in Strenge nur auf homogene Lösungen anwenden; zur Deutung des Geschehens in komplex zusammengesetzten und durch Kompartimentgrenzen unterteilten zellulären Strukturen ist man auf die Hilfe mehr oder weniger modellhafter Vorstellungen angewiesen, um den Verlauf einer radikalischen Reaktion zu beschreiben.

Aus den für Radikale typischen Reaktionscharakteristika lassen sich die folgenden allgemein gültigen Aussagen ableiten: Unter den in vivo herrschenden Bedingungen sind radikalische Kettenreaktionen sowohl im intra- wie auch im extrazellulären Bereich auf in Relation zu zellulären Dimensionen relativ kleine Bezirke beschränkt. Durch Reaktion mit den in der Zelle, in der Interstitialflüssigkeit oder im Blut gelösten Substanzen entstehen aus den primären Radikalen innerhalb kurzer Diffusionsstrecken andere radikalische Kettenträger und die für Radikalreaktionen charakteristischen peroxidischen Endprodukte. Erst die als Folge des primären radikalischen Prozesses entstehenden Peroxide sind relativ frei diffusibel und können mit spezifischen Targets — z.B. Bindungsstellen für Übergangsmetallionen — unter Bildung neuer Radikale reagieren. Damit läßt sich erklären, daß Radikalreaktionen, obwohl sie im Prinzip unspezifisch sind, letzten Endes doch zu ortsspezifischen Effekten fuhren können. Radikale per se sind nur unter ganz speziellen Voraussetzungen in der Lage, Kompartimentgrenzen zu überschreiten. Da aber viele ihrer peroxidischen Folgeprodukte membrangängig sind, kann es zu grenzüberschreitenden Sekundärreaktionen kommen, die in ihren chemischen Folgen von radikalischen Primärreaktionen nicht zu unterscheiden sind.

Radikalreaktionen müssen nicht notwendigerweise schädigend sein, sondern können auch — im teleologisch positiven Sinne — von der Zelle zu metabolischen und synthetischen Leistungen herangezogen werden.

Unter den Nachweismethoden eröffnen nur die aufwendigen, mehr physikalisch orientierten, Verfahren der Pulsradiolyse und der Elektronen-Spinresonanz-Spektroskopie die Möglichkeit, Radikale direkt zu identifizieren. Wegen der auftretenden schnellen Reaktionen sind chemische Nachweisverfahren mehr oder weniger darauf angewiesen, Endprodukte radikalischer Kettenreaktionen zu erfassen und daraus indirekte Schlüsse zu ziehen. Diese Schlüsse müssen durch den Einsatz spezifischer Radikalfänger überprüft und verifiziert werden. Ferner sind die Nachweismethoden zu modifizieren, je nachdem, ob intrazellulär generierte Radikale detektiert werden sollen oder ob Information gewünscht wird über Art und Ausbeute von Radikalen, die sekretiert oder extrazellulär gebildet wurden.

Summary

The attempt to extrapolate radiation chemical in vitro-data of radical reactions to the in vivo-situation meets with severe restrictions. The laws of chemical kinetics are strictly valid only in homogeneous solutions; to arrive at a proper description of radical reactions in complex cellular environments being subdivided by compartment boundaries, one has to rely on model conceptions. From the characteristics which are typical for radical reactions the following statements of general validity may be derived: under the conditions prevailing in vivo, radical chain reactions are intracellularly as well as extracellularly confined to rather limited spatial areas with regard to cellular dimensions. Within short diffusion distances they are bound to react with cellular components, with interstitial fluid or with substances dissolved in the blood, producing radical chain carriers and those peroxidic products which are characteristic for aerobic chain reactions. Only these peroxides are able to diffuse rather freely and thus may react with specific targets — e.g. binding sites of transition metals — to initiate secondary radical chains. This explains why radicals, even though their reactions are intrinsically unspecific, are able to exert “site specific” effects. Only under very special conditions radicals proper are able to cross compartment boundaries. As many of their their peroxidic products are able to do so, nevertheless secondary reactions may occur, which are chemically not discernible from their primary counterpart.

Radical reactions are not necessarily deleterious but can also be used by the cell to fulfill teleogically meaningful metabolic or synthetic purposes.

Amongst the identification methods for radical reactions only the physical procedures of pulse radiolysis and Electron-Spinresonance Spectroscopy offer the possibility to identify radicals directly. Owing to the inherent velocity of radical reactions analytical procedures have to rely on the identification of endproducts of the pertinent chain reactions and to arrive at conclusions in an indirect way. These conclusions must then be corroborated by application of specific scavengers. Furthermore the detection methods have to be modified depending on the goal of either identifying intracellularly generated radicals or of quantifying radicals which are secreted or formed extracellularly.

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Literatur

  1. 1.
    Beyer W, Imlay J, Fridovich I (1991) Superoxide dismutases. Progr Nucleic Acid Res Mol Biol 40:221–253.CrossRefGoogle Scholar
  2. 2.
    Bielski BHJ, Arudi RL, Sutherland MW (1983) A study of the reactivity of HO2/O2 with unsaturated fatty acids. J Biol Chem 258:4759–4761.PubMedGoogle Scholar
  3. 3.
    Bielski BHJ, Arudi RL, Cabelli DE, Bors W (1984) Reevaluation of the reactivity of hydroxylamine with O2 /HO2. Anal Biochem 142:207–209.PubMedCrossRefGoogle Scholar
  4. 4.
    Bors W, Saran M, Michel C, Tait D (1984) Formation and reactivities of oxygen free radicals in: Breccia A, Greenstock CL, Tamba M (eds) Advances on Oxygen Radicals and Radioprotectors. Lo Scarabeo, Bologna, pp 13–27.Google Scholar
  5. 5.
    Czapski G (1984) On the use of OH scavengers in biological systems. Israel J Chem 24:29–32.Google Scholar
  6. 6.
    Elstner EF, Heupel A (1976) Inhibition of nitrite formation from hydroxylammoniumchloride: a simple assay for SOD. Anal Biochem 70:616–620.PubMedCrossRefGoogle Scholar
  7. 7.
    Forum articles (1987) Free Radic Biol Med 3:317–361.CrossRefGoogle Scholar
  8. 8.
    Greenwald RA (ed) (1985) CRC Handbook of methods in oxygen radical research. CRC, Boca Raton.Google Scholar
  9. 9.
    Imlay JA, Fridovich I (1991) Assay of metabolic superoxide production in E. coli. J Biol Chem 266:6957–6965.PubMedGoogle Scholar
  10. 10.
    Ji LL, Fu R (1992) Responses of glutathione system and antioxidant enzymes to exhaustive exercise and hydroperoxide. J Appl Physiol 72:549–554.PubMedGoogle Scholar
  11. 11.
    Kass GEN, Nicotera P, Orrenius S (1992) Calcium-modulated cellular effects of oxidants. In Cochrane CG, Gimbrone MA (eds) Biological Oxidants: Generation and Injurious Consequences. Cell Mol Mechan Inflamm. Academic Press, San Diego, pp 4:133–156.Google Scholar
  12. 12.
    Kuijk FJGM van, Sevanian A, Handelman GJ, Dratz EA (1987) A new role for phospholipase A2: protection of membranes from lipid peroxidation damage. Trends Biochem Sci 12:31–34.CrossRefGoogle Scholar
  13. 13.
    Miki M, Tamai H, Mino M, Yamamoto Y, Niki E (1987) Free radial chain oxidation of rat red blood cells by molecular oxygen and its inhibition by α-tocopherol. Arch Biochem Biophys 258:373–380.PubMedCrossRefGoogle Scholar
  14. 14.
    Nagano T, Fridovich I (1985) The co-oxidation of ammonia to nitrite during aerobic XOD reaction. Arch Biochem Biophys 241:596–601.PubMedCrossRefGoogle Scholar
  15. 15.
    Packer L (ed) (1984) Methods in enzymolgy, Vol 105. Oxygen radicals in biological systems, Part D. Academic Press, New York.Google Scholar
  16. 16.
    Packer L (ed) (1994) Methods in enzymolgy, Vol 233. Oxygen radicals in biological systems, Part C. Academic Press, San Diego.Google Scholar
  17. 17.
    Packer L (ed) (1994) Methods in enzymolgy, Vol 234. Oxygen radicals in biological systems, Part D. Academic Press, San Diego.Google Scholar
  18. 18.
    Packer L, Glazer AN (eds) (1990) Methods in enzymolgy, Vol 186. Oxygen radicals in biological systems, Part B. Academic Press, New York.Google Scholar
  19. 19.
    Ross AB, Mallard WG, Helman WP, Buxton GV, Huie RE, Neta P (1994) NDRL-NIST Solution kinetics Database — Ver 2. NIST Standard Reference Data, Gaithersburg, MD.Google Scholar
  20. 20.
    Saran M, Bors W (1989) Oxygen radicals acting as chemical messengers: a hypothesis. Free Rad Res Comm 7:213–220.CrossRefGoogle Scholar
  21. 21.
    Saran M, Bors W (1990) Radical reactions in vivo — an overview. Radiat Environ Biophys 29:249–262.PubMedCrossRefGoogle Scholar
  22. 22.
    Schreck R, Baeuerle PA (1991) A role for oxygen radicals as second messengers. Trends Cell Biol 1:39–42.PubMedCrossRefGoogle Scholar
  23. 23.
    Sott JA, Rabito CA (1988) Oxygen radicals and plasma membrane potential. Free Rad Biol Med 5:237–246.CrossRefGoogle Scholar
  24. 24.
    Sies H (ed) (1991) Oxidative Stress: Oxidants and Antioxidants. Academic Press, London.Google Scholar
  25. 25.
    Witt EH, Reznick AZ, Viguie CA, Starke-Reed P, Packer L (1992) Exercise, oxidative damage and effects of antioxidant manipulation. J Nutr 122:766–773.PubMedGoogle Scholar
  26. I.
    Packer L (ed) (1984) Methods in enzymology. Vol 105. Oxygen radicals in biological systems. Academic Press, New York.Google Scholar
  27. II.
    Packer L, Glazer AN (eds) (1990) Methods in enzymology. Vol 186. Oxygen radicals in biological systems, Part B. Academic Press, New York.Google Scholar
  28. III.
    Packer L (ed) (1994) Methods in enzymology. Vol 233. Oxygen radicals in biological systems, Part C. Academic Press, San Diego.Google Scholar
  29. IV.
    Packer L (ed) (1994) Methods in enzymology. Vol 234. Oxygen radicals in biological systems, Part D. Academic Press, San Diego.Google Scholar
  30. V.
    Greenwald RA (ed) (1985) CRC Handbook of methods in oxygen radical research CRC, Boca Raton.Google Scholar
  31. 1a.
    Asmus KD (1984) Pulse radiolysis methodology. In I: pp 167-178.Google Scholar
  32. 1a.
    Saran M, Vetter G, Erben-Russ M, Winter R, Kruse A, Michel C, Bors W (1987) Pulse radiolysis equipment a setup for simultaneous multiwavelength kinetic spectroscopy. Rev Sci Instrum 58:363–368.CrossRefGoogle Scholar
  33. 1a.
    Sonntag C von, Schuchmann HP (1994) Pulse radiolysis. In III: pp 3-20.Google Scholar
  34. 1b.
    Mason RP, Knecht KT (1994) In vivo detection of radical adducts by electron spin resonance. In III: pp 112-117.Google Scholar
  35. 1b.
    Buettner GR, Mason RP (1990) Spin-trapping methods for detecting super-oxide and hydroxyl free radicals in vitro and in vivo. In II: pp 127-133.Google Scholar
  36. 1b.
    Janzen EG (1990) Spin trapping and associated vocabulary. Free Radic Res Commun 9:163–167.PubMedCrossRefGoogle Scholar
  37. 1b.
    Rosen GM, Pou S, Britigan BE, Myron SC (1994) Spin trapping of hydroxyl radicals in biological systems. In III: pp 105-111.Google Scholar
  38. 2a.
    Gotoh N, Niki E (1994) Measurement of superoxide reaction by chemiluminescence. In III: pp 154-160.Google Scholar
  39. 2a.
    Murphy ME, Sies H (1990) Visible-range low-level chemiluminescence in biological systems. In II: pp 595-610.Google Scholar
  40. 2a.
    Nakano M (1990) Assay for SOD based on chemiluminescence of luciferin analog. In II: pp 222-231.Google Scholar
  41. 2b.
    Fridovich I (1985) Cytochrome C. In V: pp 121-122.Google Scholar
  42. 2c.
    Auclair C, Voisin E (1985) Nitroblue tetrazolium reduction. In V: pp 123-132.Google Scholar
  43. 2d.
    Elstner EF, Heupel A (1976) Inhibition of nitrite formation from hydroxylammoniumchloride: a simple assay for SOD. Anal Biochem 70:616–620.PubMedCrossRefGoogle Scholar
  44. 2d.
    Bors W, Lengfelder E, Saran M, Michel C, Fuchs C, Frenzel C (1977) Oxidation of hydroxylamine to nitrite as an assay for the combined presence of superoxide anions and hydroxyl radicals. Biochem Biophys Res Commun 75:973–979.PubMedCrossRefGoogle Scholar
  45. 2d.
    Bielski BHJ, Arudi RL, Cabelli DE, Bors W (1984) Reevaluation of the reactivity of hydroxylamine with O2 /HO2. Anal Biochem 142:207–209.PubMedCrossRefGoogle Scholar
  46. 2e.
    Saran M, Bors W, Michel C, Elstner EF (1980) Formation of ethylene from methionine. Reactivity of radiolytically produced oxygen radicals and effect of substrate activation. Int J Radiat Biol 37:521–527.CrossRefGoogle Scholar
  47. 2e.
    Youngman RJ, Elstner EF (1985) Ethylene formation from methionine in the presence of pyridoxal phosphate. In V: pp 165-168.Google Scholar
  48. 2f.
    Winston GW, Cederbaum AI (1985) Decarboxylation of 14C-benzoic acid. In V: pp 169-175.Google Scholar
  49. 2g.
    Halliwell B, Gutteridge JMC (1985) Hydroxyl radicals assayed by aromatic hydroxylation and deoxyribose degradation. In V: pp 177-180.Google Scholar
  50. 2g.
    Aruoma OI (1994) Deoxyribose assay for detecting hydroxyl radicals. In III: pp 57-66.Google Scholar
  51. 2h.
    Babbs CF, Steiner MG (1990) Detection and quantitation of hydroxyl radical using DMSO as molecular probe. In II: pp 137-147.Google Scholar
  52. 2i.
    Misra HP, Fridovich I (1972) The role of O2 in the autoxidation of epinephrine and a simple assay for SOD. J Biol Chem 247:3170–75.PubMedGoogle Scholar
  53. 2i.
    Bors W, Saran M, Michel C, Lengfelder E, Fuchs C, Spoettl, R (1975) Pulse radiolytic investigations of catechols and catecholamines. I. Adrenaline and adrenochrome. Int J Radiat Biol 28:353–371.CrossRefGoogle Scholar
  54. 2k.
    Bors W, Saran M, Michel C (1982) Radical intermediates involved in the bleaching of the carotenoid crocin. OH radicals, O2 and (e)aq. Int J Radiat Biol 41:493–501.CrossRefGoogle Scholar
  55. 2k.
    Bors W, Michel C, Saran M (1984) Inhibition of the bleaching of the carotenoid crocin. A rapid test for quantifying antioxidant activity. Biochim Biophys Acta 796:312–319.Google Scholar
  56. 2l.
    Jessup W, Dean RT, Gebicki JM (1994) Iodometric determination of hydroperoxides in lipids and proteins. In III: pp 289-303.Google Scholar
  57. 2l.
    van Kuijk FJGM, Thomas DW, Stephens RJ, Dratz EA (1990) GC-MS assays for lipid peroxides. In II: pp 388-398.Google Scholar
  58. 2l.
    Iwaoka T, Tabata F, Takahashi T (1987) Lipid peroxidation and lipid peroxide detected by chemiluminescence. Free Rad Biol Med 3:329–333.PubMedCrossRefGoogle Scholar
  59. 2l.
    Miyazawa T, Fujimoto K, Suzuki T, Yasuda K (1994) Determination of phospholipid hydroperoxides using luminol chemiluminescence-high-perfor-mance liquid chromatography. In III: pp 324-332.Google Scholar
  60. 2l.
    Sattler W, Mohr D, Stocker R (1994) Rapid isolation of lipoproteins and assessment of their peroxidation by high performance liquid chromatography postcolumn chemiluminescence. In III: pp 469-489.Google Scholar
  61. 2l.
    Yamamoto Y (1994) Chemiluminescence-based high-performance liquid chromatography assay of lipid hydroperoxides. In III: pp 319-324.Google Scholar
  62. 2l.
    Meguro H, Akasaka K, Ohrui H (1990) Determination of hydroperoxides with fluorometric reagent diphenyl-1-pyrenyl-phosphine. In II: pp 157-160.Google Scholar
  63. 2m.
    Gutteridge JMC (1986) Aspects to consider when detecting and measuring lipid peroxidation. Free Rad Res Comm 1:173–184.CrossRefGoogle Scholar
  64. 2m.
    Bird RP, Draper HH (1984) Comparative studies on different methods of malonaldehyde determination. In I: pp 299-305.Google Scholar
  65. 2m.
    Knight JA, Pieper RK, McClellan L (1988) Specificity of the thiobarbituric acid reaction: its use in studies of lipid peroxidation. Clin Chem 34:2433–38.PubMedGoogle Scholar
  66. 2m.
    Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. In II: pp 407-420.Google Scholar
  67. 2m.
    Chirico S (1994) High-performance liquid chromatography-based thiobarbituric acid tests, In III: pp 314-318.Google Scholar
  68. 2m.
    Cueto R, Squadrito GL, Pryor WA (1994) Quantifying aldehydes and distinguishing aldehydic product profiles from autoxidation and ozonation of unsaturated fatty acids. In III: pp 174-182.Google Scholar
  69. 2n.
    Lawrence GD, Cohen G (1984) Concentrating ethane from breath to monitor lipid peroxidation in vivo. In I: pp 305-311.Google Scholar
  70. 2n.
    Mueller A, Sies, H (1984) Assay of ethane and pentane from isolated organs and cells. In I: pp 311-319.Google Scholar
  71. 2n.
    Remmer H, Gharaibeh A (1984) Measurement of the oxidation rate of volatile alkanes: a new and non-invasive procedure for testing the drug-metabolizing capacity of the liver. Biochem Soc Trans 12:28–30.PubMedGoogle Scholar
  72. 2q.
    Ansari GAS, Smith LS (1994) Assay of cholesterol autoxidation, In III: 332-338.Google Scholar
  73. 2r.
    Pacifici RE, Davies KJA (1990) Protein degradation as an index of oxidative stress. In II: pp 485-501.Google Scholar
  74. 2r.
    Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz A, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. In II: pp 464-477.Google Scholar
  75. 2r.
    Levine RL, Williams JA, Stadtman ER, Shacter E (1994) Carbonyl assays for determination of oxidatively modified proteins. In III: pp 346-357.Google Scholar
  76. 2r.
    Kalef E, Gitler C (1994) Purification of vicinal dithiol-containing proteins by arsenical-based affinity chromatography. In III: pp 395-403.Google Scholar
  77. 2r.
    Mitton KP, Trevithick JR (1994) High-performance liquid chromatography-electrochemical detection of antioxidants in vertebrate lens; glutathione, tocopherol, and ascorbate. In III: pp 523-539.Google Scholar
  78. 2r.
    Thomas JA, Chai YC, Jung CH (1994) Protein S-thiolation and dethiolation. In III: pp 385-395.Google Scholar
  79. 2s.
    Birnboim HC (1990) Fluorometric analysis of DNA unwinding to study strand breaks and repair in mammalian cells. In II: pp 550-554.Google Scholar
  80. 2s.
    Dizdaroglu M, Gajewski E (1990) Selected-ion mass spectrometry: assays of oxidative DNA damage. In II: pp 530-544.Google Scholar
  81. 2s.
    Hayes JJ, Kam L, Tullius TD ( 1990) Footprinting protein-DNA complexes with gamma-rays. In II: pp 545-549.Google Scholar
  82. 2s.
    Lown JW (1984) Ethidium binding assay for reactive oxygen species generated from reductively activated adriamycin (doxorubicin). In I: pp 532-539.Google Scholar
  83. 2s.
    Sonntag C von, Schuchmann HP (1990) Radical-mediated DNA damage in presence of oxygen. In II: pp 511-520.Google Scholar
  84. 3a.
    Hsie AW, Recio L, Katz DS, Lee CQ, Wagner M, Schenley RL (1986) Evidence for reactive oxygen species inducing mutations in mammalian cells. Proc Nat Acad Sci USA 83:9616–20.PubMedCrossRefGoogle Scholar
  85. 3a.
    Shigenaga MK, Park JW, Cundy KC, Gimeno CJ, Ames BN (1990) In vivo oxidative DNA damage: measurement of 8-hydroxy-2′-deoxyguanosine in DNA and urine by HPLC with electrochemical detection. In II: pp 521-529.Google Scholar
  86. 3a.
    Häring M, Rüdiger H, Demple B, Boiteux S, Epe B (1994) Recognition of oxidized abasic sites by repair endonucleases. Nucleic Acid Res 22:2010–2015.PubMedCrossRefGoogle Scholar
  87. 3b.
    Dellarco VL, Voytek PE, Hollaender A (eds) (1985) Aneuploidy. Plenum, New York.Google Scholar
  88. 3b.
    Polak JM, McGee J O’D (eds) (1990) In situ hybridization: Principles and practice. Oxford Univ. Press, Oxford.Google Scholar
  89. 3c.
    Melamed MR, Lindmo T, Mendelsohn ML (eds) (1990) Flow cytometry and sorting. 2. edn. Wiley-Liss, New York.Google Scholar
  90. 3c.
    Arrio B, Arrio M, Bonnefont-Rousselot D, Catudioc JD, Packer L (1994) Assaying low density lipoprotein oxidation by laser light scattering. In III: pp 453-459.Google Scholar
  91. 3c.
    Bass DA, Parce JW, Dechatlet JR, Szeijda P, Seeds MC, Thomas M (1983) Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulation. J Immunol 130:1510–1517.Google Scholar
  92. 3c.
    Menzel DB, Vandagriff R, Ziegler B (1990) Imaging of reactive oxygen species in living lung cells exposed to oxidizing air pollutants. Free Rad Biol Med 9. [Suppl 1]:Abstract 12.7.Google Scholar
  93. 3c.
    Rothe G, Valet G (1994) Flow cytometric assays of oxidative burst activity in phagocytes. In III: pp 539-548.Google Scholar
  94. 3d.
    Scott JA, Fischman AJ, Homcy CJ, Fallon JT, Khaw BA, Peto CA, Rabito CA (1989) Morphologic and functional correlates of plasma membrane injury during oxidant exposure. Free Rad Biol Med 6:361–367.PubMedCrossRefGoogle Scholar
  95. 3d.
    Scott JA, Rabito CA (1988) Oxygen radicals and plasma membrane potential. Free Rad Biol Med 5:237–246.PubMedCrossRefGoogle Scholar
  96. 3d.
    Fuchs J, Zimmer G, Thürich T, Bereiter-Hahn J, Packer L (1990) Noninvasive fluorometric measurement of mitochondrial membrane potential in isolated working rat hearts during ischemia and reperfusion. In II: pp 723-728.Google Scholar
  97. 3d.
    Hearse DJ, Kusama Y, Bernier M (1989) Rapid electrophysiological changes leading to arrhythmias in the aerobic rat heart. Photosensitization studies with rose bengal-derived reactive oxygen intermediates. Circul Res 65:146–153.Google Scholar
  98. 3e.
    Babbs CF (1994) Histochemical methods for localization of endothelial super-oxide and hydrogen peroxide generation in perfused organs. In III: pp 619-630.Google Scholar
  99. 3e.
    Ravindranath V (1994) Animal models and molecular markers for cerebral ischemia-reperfusion injury in brain. In III: pp 610-619.Google Scholar
  100. 3e.
    Seeger W, Walmrath D, Grimminger F, Rosseau S, Schütte H, Krämer HJ, Ermert L, Kiss L (1994) Adult respiratory distress syndrome: model systems using isolated perfused rabbit lungs, In III: pp 549-585.Google Scholar
  101. 3e.
    Shuter SL, Davies MJ, Garlick PB, Hearse DJ, Slater TF (1990) Studies on the effects of antioxidants and inhibitors of radical generation on free radical production in the reperfused rat heart using ESR spectroscopy. Free Rad Res Comm 9:223–232.CrossRefGoogle Scholar
  102. 3e.
    Sussman MS, Bulkley GB (1990) Oxygen-derived free radicals in reperfusion injury. In II: pp 711-722.Google Scholar
  103. 3f.
    Groot H de (1990) Oxystat technique in the study of reactive oxygen species. In II: pp 443-447.Google Scholar
  104. 3g.
    Crawford DR, Edbauer-Nechamen CA, Lowry CV, Salmon SL, Kim YK, Davies J, Davies KJA (1994) Assessing gene expression during oxidative stress. In IV: pp 175-217.Google Scholar
  105. 3g.
    Storz G, Altuvia S (1994) OxyR regulon. In IV: pp 217-224.Google Scholar
  106. 3g.
    Schreck R, Baeuerle PA (1994) Assessing oxygen radicals as mediators in activation of inducible eukaryotic transcription factor NF-κB. In IV: pp 151-163.Google Scholar

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