Measurements in vivo of parameters pertinent to ROS/RNS using EPR spectroscopy

  • Nadeem Khan
  • Harold Swartz
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


The technique ofin vivoEPR spectroscopy can provide useful and even unique information pertinent to the study of oxygen/ nitrogen radicals and related processes. The parameters that can be measured include: (a) Oxygen centered radicals (by spin trapping); (b) carbon centered radicals (by spin trapping and sometimes by direct observation); (c) sulfur centered radicals (by spin trapping and sometimes by direct observation); (d) nitric oxide (by spin trapping); (e) oxygen (using oxygen sensitive paramagnetic materials); (f) redox state (using metabolism of nitroxides); (g) thiol groups (using special nitroxides); (h) pH (using special nitroxides); (h) perfusion (using washout of paramagnetic tracers); (i) some redox active metal ions (chromium, manganese). The current state of the art for these and other measurements is discussed, especially in relationship to experiments that are likely to be useful for studies of reactive oxygen species (ROS) and/or reactive nitrogen species (RNS). (Mol Cell Biochem 234/235:341-357, 2002)

Key words

reactive oxygen species (ROS) reactive nitrogen species (RNS) reactive sulfur species (RSS) p02pH pH nitroxides metal ions spin trapping in vivo EPR 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mader K, Stosser R, Borchert HH: Detection of free radicals in living mice after inhalation of DTBN by X-band ESR. Free Radic Biol Med 14: 339–342, 1993PubMedCrossRefGoogle Scholar
  2. 2.
    Zweier JL, Flaherty JT, Weisfeldt ML: Direct measurement of free radical generation following reperfusion of ischemic myocardium. Proc Natl Acad Sci USA 84: 1404–1407, 1987PubMedCrossRefGoogle Scholar
  3. 3.
    Baker JE, Felix CC, Olinger GN, Kalyanaraman B: Myocardial ischemia and reperfusion: Direct evidence for free radical generation by electron spin resonance spectroscopy. Proc Natl Acad Sci USA 85: 2786–2789, 1988PubMedCrossRefGoogle Scholar
  4. 4.
    Nakazawa H, Ichimori K, Shinozaki Y, Okino H, Hori S: Is superoxide demonstration by electron-spin resonance spectroscopy really superoxide? Am J Physiol 255: H213—H215, 1988Google Scholar
  5. 5.
    Lai EK, Crossley C, Sridhar R, Misra HP, Janzen EG, McCay PB:In vivospin trapping of free radicals generated in brain, spleen, and liver during gamma radiation of mice. Arch Biochem Biophys 244: 156–160, 1986Google Scholar
  6. 6.
    Burkitt MJ, Mason RP: Direct evidence forin vivohydroxyl-radical generation in experimental iron overload: An ESR spin-trapping investigation. Proc Natl Acad Sci USA 88: 8440–8444, 1991PubMedCrossRefGoogle Scholar
  7. 7.
    Knecht KT, Mason RP:In vivospin trapping of xenobiotic free radical metabolites. Arch Biochem Biophys 303: 185–194, 1993PubMedCrossRefGoogle Scholar
  8. 8.
    Blasig IE, Ebert B, Love H: Effect of activated oxygen species on mitochondria isolated from myocardium after reperfusion injury. Stud Biophys 116: 35–42, 1986Google Scholar
  9. 9.
    Gutteridge JM: Free radicals in disease processes: A compilation of cause and consequence. Free Radic Res Commun 19: 141–158, 1993PubMedCrossRefGoogle Scholar
  10. 10.
    Knight JA: Diseases related to oxygen-derived free radicals. Ann Clin Lab Sci 25: 111–121, 1995PubMedGoogle Scholar
  11. 11.
    Satriano JA, Shuldiner M, Hora K, Xing Y, Shan Z, Schlondorff D: Oxygen radicals as second messengers for expression of the monocyte chemoattractant protein, JE/MCP-1, and the monocyte colony-stimulating factor, CSF-1, in response to tumor necrosis factor-alpha and immunoglobulin G. Evidence for involvement of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent oxidase. J Clin Invest 92: 1564–1571, 1993PubMedCrossRefGoogle Scholar
  12. 12.
    Joseph JA, Cutler RC: The role of oxidative stress in signal transduction changes and cell loss in senescence. Ann NY Acad Sci 738: 37–43, 1994Google Scholar
  13. 13.
    Remick DG, Villarete L: Regulation of cytokine gene expression by reactive oxygen and reactive nitrogen intermediates. J Leukoc Biol 59: 471–475, 1996PubMedGoogle Scholar
  14. 14.
    Hancock JT: Superoxide, hydrogen peroxide and nitric oxide as signaling molecules: Their production and role in disease. Br J Biomed Sci 54: 38–46, 1997PubMedGoogle Scholar
  15. 15.
    Flescher E, Tripoli H, Salnikow K, Burns FJ: Oxidative stress suppresses transcription factor activities in stimulated lymphocytes. Clin Exp Immunol 112: 242 247, 1998Google Scholar
  16. 16.
    Poderoso JJ, Boveris A, Cadenas E: Mitochondrial oxidative stress: A self-propagating process with implications for signaling cascades. Biofactors 11: 43–45, 2000PubMedCrossRefGoogle Scholar
  17. 17.
    Griendling KK, Sorescu D, Lassegue B, Ushio-Fukai M: Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 20: 2175–2183, 2000PubMedCrossRefGoogle Scholar
  18. 18.
    Bauer G: Reactive oxygen and nitrogen species: Efficient, selective, and interactive signals during intercellular induction of apoptosis. Anticancer Res 20: 4115–4139, 2000PubMedGoogle Scholar
  19. 19.
    Camougrand N, Rigoulet M: Aging and oxidative stress: Studies of some genes involved both in aging and in response to oxidative stress. Resp Physiol 128: 393–401, 2001CrossRefGoogle Scholar
  20. 20.
    Sauer H, Wartenberg M, Hescheler J: Reactive oxygen species as intracellular messengers during cell growth and differentiation. Cell.Physiol Biochem 11: 173–186, 2001PubMedCrossRefGoogle Scholar
  21. 21.
    Carmody RJ, Cotter TG: Signaling apoptosis: A radical approach. Redox Rep 6: 77–90, 2001PubMedCrossRefGoogle Scholar
  22. 22.
    Janzen EG: Spin trapping. Meth Enzymol 105: 188–198, 1984PubMedCrossRefGoogle Scholar
  23. 23.
    Britigan BE, Cohen MS, Rosen GM: Detection of the production of oxygen-centered free radicals by human neutrophils using spin trapping techniques: A critical perspective. J Leukoc Biol 41: 349–362, 1987PubMedGoogle Scholar
  24. 24.
    Buettner GR, Mason RP: Spin-trapping methods for detecting superoxide and hydroxyl free radicalsin vitroandin vivo.Meth Enzymol 186: 127–133, 1990PubMedCrossRefGoogle Scholar
  25. 25.
    Berliner U, Khramtsov V, Fujii H, Clanton TL: Uniquein vivoapplications of spin traps. Free Radic Biol Med 30: 489–499, 2001PubMedCrossRefGoogle Scholar
  26. 26.
    Finkelstein E, Rosen GM, Rauckman EJ: Spin trapping of superoxide and hydroxyl radical.Practical aspects. Arch Biochem Biophys 200:1–16,1980PubMedCrossRefGoogle Scholar
  27. 27.
    Mason RP, Knecht KT:In vivodetection of radical adducts by electron spin resonance. Meth Enzymol 233: 112–117, 1994PubMedCrossRefGoogle Scholar
  28. 28.
    Hojo Y, Okado A, Kawazoe S, Mizutani T: Direct evidence forin vivohydroxyl radical generation in blood of mice after acute chromium(VI) intake: Electron spin resonance spin-trapping investigation. Biol Trace Elem Res 76: 75–84, 2000PubMedCrossRefGoogle Scholar
  29. 29.
    Roubaud V, Sankarapandi S, Kuppusamy P, Tordo P, Zweier JL: Quantitative measurement of superoxide generation using the spin trap 5(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide. Anal Biochem 247: 404–411, 1997PubMedCrossRefGoogle Scholar
  30. 30.
    Liu KJ, Miyake M, Panz T, Swartz H: Evaluation of DEPMPO as a spin trapping agent in biological systems. Free Radic Biol Med 26: 714–721, 1999PubMedCrossRefGoogle Scholar
  31. 31.
    Timmins GS, Liu KJ, Bechara EJ, Kotake Y, Swartz HM: Trapping of free radicals with directin vivoEPR detection: A comparison of 5,5dimethyl-l -pyrroline-N-oxide and 5-diethoxyphosphoryl-5-methyl-l -pyrroline-N-oxide as spin traps for HO’ and SO4‘. Free Radic Biol Med 27: 329–333, 1999PubMedCrossRefGoogle Scholar
  32. 32.
    Stolze K, Udilova N, Nohl H: Spin trapping of lipid radicals with DEPMPO-derived spin traps: Detection of superoxide, alkyl and alkoxyl radicals in aqueous and lipid phase. Free Radic Biol Med 29: 1005–1014, 2000PubMedCrossRefGoogle Scholar
  33. 33.
    Olive G, Mercier A, Le Moigne F, RockenbauerA, Tordo P: 2-ethoxycarbonyl-2-methyl-3,4-dihydro-2H-pyrrole-l-oxide: Evaluation of the spin trapping properties. Free Radic Biol Med 28: 403–408, 2000PubMedCrossRefGoogle Scholar
  34. 34.
    Zhang H, Joseph J, Vasquez-Vivar J, Karoui H, Nsanzumuhire C, Martasek P, Tordo P, Kalyanaraman B: Detection of superoxide anion using an isotopically labeled nitrone spin trap: Potential biological applications. FEBS Lett 473: 58–62, 2000PubMedCrossRefGoogle Scholar
  35. 35.
    Zhao H, Joseph J, Zhang H, Karoui H, Kalyanaraman B: Synthesis and biochemical applications ofa solid cyclic nitrone spin trap: A relatively superior trap for detecting superoxide anions and glutathiyl radicals. Free Radic Biol Med 31: 599–606, 2001PubMedCrossRefGoogle Scholar
  36. 36.
    Tordo P: Spin-trapping: Recent developments and applications. Electron Paramag Res 16: 116–144, 1998CrossRefGoogle Scholar
  37. 37.
    Samuni A, Samuni A, Swartz HM: The cellular-induced decay of DMPO spin adducts of *OH and.02. Free Radic Biol Med 6: 179–183, 1989PubMedCrossRefGoogle Scholar
  38. 38.
    Eaton GR: A new EPR methodology for the study of biological systems. Biophys J 64: 1373–1374, 1993PubMedCrossRefGoogle Scholar
  39. 39.
    Ishida S, Matsumoto S, Yokoyama H, Mori N, Kumashiro H, Tsuchihashi N, Ogata T, Yamada M, Ono M, Kitajima T: An ESR-CT imaging of the head ofa living rat receiving an administration ofa nitroxide radical. Mag Res Imaging 10: 109–114, 1992CrossRefGoogle Scholar
  40. 40.
    Swartz HM, Walczak T: Developingin vivoEPR oximetry for clinical use. Adv Exp Med Biol 454: 243–252, 1998PubMedCrossRefGoogle Scholar
  41. 41.
    Liu KJ, Shi X, Jiang JJ, Goda F, Dalai N, Swartz HM: Chromate-induced chromium(V) formation in live mice and its control by cellular antioxidants: An L-band electron paramagnetic resonance study. Arch Biochem Biophys 323: 33–39, 1995PubMedCrossRefGoogle Scholar
  42. 42.
    Jiang JJ, Liu KJ, Jordan SJ, Swartz HM, Mason RP: Detection of free radical metabolite formation usingin vivoEPR spectroscopy: Evidence of rat hemoglobin thiyl radical formation following administration of phenylhydrazine. Arch Biochem Biophys 330: 266–270, 1996PubMedCrossRefGoogle Scholar
  43. 43.
    Liu KJ, Shi X, Jiang J, Goda F, Dalai N, Swartz HM: Low frequency electron paramagnetic resonance investigation on metabolism of chromium(VI) by whole live mice. Ann Clin Lab Sci 26: 176–184, 1996PubMedGoogle Scholar
  44. 44.
    Frejaville C, Karoui H, Tuccio B, Le Moigne F, Culcasi M, Pietri S, Lauricella R, Tordo P: 5-(Diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide: A new efficient phosphorylated nitrone for thein vitroandin vivospin trapping of oxygen-centered radicals. J Med Chem 38: 258–265, 1995Google Scholar
  45. 45.
    Karoui H, Nsanzumuhire C, Le Moigne F, Tordo P: Synthesis ofa New Spin Trap: 2-(Diethoxyphosphoryl)-2-phenyl-3,4-dihydro-2H-pyrrole 1-Oxide. J Org Chem 64: 1471–1477, 1999PubMedCrossRefGoogle Scholar
  46. 46.
    Halpern HJ, Yu C, Barth E, Peric M, Rosen GM:In situdetection, by spin trapping, of hydroxyl radical markers produced from ionizing radiation in the tumor ofa living mouse. Proc Natl Acad Sci USA 92: 796–800, 1995PubMedCrossRefGoogle Scholar
  47. 47.
    Kadiiska MB, Burkitt MJ, Xiang QH, Mason RP: Iron supplementation generates hydroxyl radicalin vivo.An ESR spin-trapping investigation. J Clin Invest 96: 1653–1657, 1995PubMedCrossRefGoogle Scholar
  48. 48.
    Miura Y, Utsumi H, Hamada A: Effects of inspired oxygen concentration onin vivoredox reaction of nitroxide radicals in whole mice. Biochem Biophys Res Commun 182: 1108–1114, 1992PubMedCrossRefGoogle Scholar
  49. 49.
    Gomi F, Utsumi H, Hamada A, Matsuo M: Aging retards spin clearance from mouse brain and food restriction prevents its age-dependent retardation. Life Sei 52: 2027–2033, 1993CrossRefGoogle Scholar
  50. 50.
    Utsumi H, Takeshita K, Miura Y, Masuda S, Hamada A:In vivoEPR measurement of radical reaction in whole mice: Influence of inspired oxygen and ischemia-reperfusion injury on nitroxide reduction. Free Radic Res Commun 19: S219–S225, 1993PubMedCrossRefGoogle Scholar
  51. 51.
    Paolini M, Pozzetti L, Pedulli GF, Cipollone M, Mesirca R, CantelliForti G: Paramagnetic resonance in detecting carcinogenic risk from cytochrome P450 overexpression. J Invest Med 44: 470–473, 1996Google Scholar
  52. 52.
    Miura Y, Hamada A, Utsumi H:In vivoESR studies of antioxidant activity on free radical reaction in living mice under oxidative stress. Free Radic Res 22: 209–214, 1995PubMedCrossRefGoogle Scholar
  53. 53.
    Miura Y, Anzai K, Takahashi S, Ozawa T: A novel lipophilic spin probe for the measurement of radiation damage in mouse brain usingin vivoelectron spin resonance (ESR) FEBS Lett 419: 99–102, 1997PubMedGoogle Scholar
  54. 54.
    Kontos HA: George E. Brown memorial lecture. Oxygen radicals in cerebral vascular injury. Cire Res 57: 508–516, 1985CrossRefGoogle Scholar
  55. 55.
    Ambrosio G, Zweier JL, Duilio C, Kuppusamy P, Santoro G, Elia PP, Tritto I, Cirillo P, Condorelli M, Chiariello M: Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J Biol Chem 268: 18532–18541, 1993PubMedGoogle Scholar
  56. 56.
    Paller MS, Jacob HS: Cytochrome P-450 mediates tissue-damaging hydroxyl radical formation during reoxygenation of the kidney. Proc Natl Acad Sci USA 91: 7002–7006, 1994PubMedCrossRefGoogle Scholar
  57. 57.
    Rao PS, Cohen MV, Mueller HS: Production of free radicals and lipid peroxides in early experimental myocardial ischemia. J Mol Cell Cardiol 15: 713–716, 1983PubMedCrossRefGoogle Scholar
  58. 58.
    Arroyo CM, Kramer JH, Dickens BF, Weglicki WB: Identification of free radicals in myocardial ischemia/reperfusion by spin trapping with nitrone DMPO. FEBS Lett 221: 101–104, 1987PubMedCrossRefGoogle Scholar
  59. 59.
    Bolli R, Patel BS, Jeroudi MO, Lai EK, McCay PB: Demonstration of free radical generation in ‘stunned’ myocardium of intact dogs with the use of the spin trap a-phenyl N-tert-butyl nitrone. J Clin Invest 82: 476–485, 1988PubMedCrossRefGoogle Scholar
  60. 60.
    Pincemail J, Defraigne JO, Franssen C, Defechereux T, Canivet JL, Philippart C, Meurisse M: Evidence ofin vivofree radical generation by spin trapping with a-phenyl N-tert-butyl nitrone during ischemia/ reperfusion in rabbit kidneys. Free Radic Res Commun 9: 181–186,1990PubMedCrossRefGoogle Scholar
  61. 61.
    McCord JM: Oxygen-derived free radicals in post-ischemic tissue injury. N Eng J Med 312: 159–163, 1985CrossRefGoogle Scholar
  62. 62.
    Togashi H, Shinzawa H, Yong H, Takahashi T, Noda H, Oikawa K, Kamada H: Ascorbic acid radical, superoxide, and hydroxyl radical are detected in reperfusion injury of rat liver using electron spin resonance spectroscopy. Arch Biochem Biophys 308: 1–7, 1994PubMedCrossRefGoogle Scholar
  63. 63.
    Janzen EG, Towner RA, Krygsman PH, Haire DL, Poyer JL: Structure identification of free radicals by ESR and GC/MS of PBN spin adducts from thein vitroandin vivorat liver metabolism of halothane. Free Radic Res Commun 9: 343–351, 1990PubMedCrossRefGoogle Scholar
  64. 64.
    Pappius HM, Wolfe LS: Functional disturbances in brain following injury: Search for underlying mechanisms. Neurochem Res 8: 63–72, 1983PubMedCrossRefGoogle Scholar
  65. 65.
    Tauber AI, Wright J, Higson FK, Edelman SA, Waxman DJ: Purification and characterization of the human neutrophil NADH-cytochrome b5 reductase. Blood 66: 673–678, 1985PubMedGoogle Scholar
  66. 66.
    Halliwell B: Oxidants and human disease: Some new concepts. FASEB J 1: 358–364, 1987PubMedGoogle Scholar
  67. 67.
    Ikeda Y, Long DM: The molecular basis of brain injury and brain edema: The role of oxygen free radicals. Neurosurgery 27: 1–11, 1990PubMedCrossRefGoogle Scholar
  68. 68.
    Sen S, Goldman H, Morehead M, Murphy S, Phillis JW: a-Phenyl-tertbutyl-nitrone inhibits free radical release in brain concussion. Free Radio Biol Med 16: 685–691, 1994CrossRefGoogle Scholar
  69. 69.
    Anderson DK, Means ED: Iron-induced lipid peroxidation in spinal cord: Protection with mannitol and methylprednisolone. J Free Radio Biol Med 1: 59–64, 1985CrossRefGoogle Scholar
  70. 70.
    Demediuk P, Saunders RD, Clendenon NR, Means ED, Anderson DK, Horrocks LA: Changes in lipid metabolism in traumatized spinal cord. Prog Brain Res 63: 211–226, 1985PubMedCrossRefGoogle Scholar
  71. 71.
    Kontos HA, Wei EP: Superoxide production in experimental brain injury. J Neurosurg 64: 803–807, 1986PubMedCrossRefGoogle Scholar
  72. 72.
    Kontos HA, Povlishock JT: Oxygen radicals in brain injury. Cent Nerv Syst Trauma 3: 257–263, 1986PubMedGoogle Scholar
  73. 73.
    Phillis JW, Sen S: Oxypurinol attenuates hydroxyl radical production during ischemia/reperfusion injury of the rat cerebral cortex: An ESR study. Brain Res 628: 309–312, 1993PubMedCrossRefGoogle Scholar
  74. 74.
    Capani F, Loidl CF, Aguirre F, Piehl L, Facorro G, Hager A, De Paoli T, Farach H, Pecci-Saavedra J: Changes in reactive oxygen species production in rat brain during global perinatal asphyxia: An ESR study. Brain Res 914: 204–207, 2001PubMedCrossRefGoogle Scholar
  75. 75.
    Stoyanovsky DA, Cederbaum AI: ESR and HPLC-EC analysis of ethanol oxidation to 1-hydroxyethyl radical: Rapid reduction and quantification of POBN and PBN nitroxides. Free Radio Biol Med 25: 536–545, 1998CrossRefGoogle Scholar
  76. 76.
    Reinke LA, Lai EK, DuBose CM, McCay PB: Reactive free radical generationin vivoin heart and liver of ethanol-fed rats: Correlation with radical formationin vitro.Proc Natl Acad Sci USA 84: 9223–9227, 1987PubMedCrossRefGoogle Scholar
  77. 77.
    Reinke LA, Lai EK, McCay PB: Ethanol feeding stimulates trichloromethyl radical formation from carbon tetrachloride in liver. Xenobiotica 18: 1311–1318, 1988PubMedCrossRefGoogle Scholar
  78. 78.
    Albano E, Tomasi A, Goria-Gatti L, Dianzani MU: Spin trapping of free radical species produced during the microsomal metabolism of ethanol. Chem Biol Interact 65: 223–234, 1988PubMedCrossRefGoogle Scholar
  79. 79.
    Knecht KT, Bradford BU, Mason RP, Thurman RG:In vivoformation of a free radical metabolite of ethanol. Mol Pharmacol 38: 26–30, 1990PubMedGoogle Scholar
  80. 80.
    Reinke LA, Kotake Y, McCay PB, Janzen EG: Spin-trapping studies of hepatic free radicals formed following the acute administration of ethanol to rats:In vivodetection of 1-hydroxyethyl radicals with PBN. Free Radio Biol Med 11: 31–39, 1991CrossRefGoogle Scholar
  81. 81.
    Bondy SC: Ethanol toxicity and oxidative stress. Toxicol Lett 63: 231–241, 1992Google Scholar
  82. 82.
    Rashba-Step J, Turro NJ, Cederbaum AI: Increased NADPH- and NADH-dependent production of superoxide and hydroxyl radical by microsomes after chronic ethanol treatment. Arch Biochem Biophys 300: 401–408, 1993PubMedCrossRefGoogle Scholar
  83. 83.
    Knecht KT, Thurman RG, Mason RP: Role of superoxide and trace transition metals in the production of alpha-hydroxyethyl radical from ethanol by microsomes from alcohol dehydrogenase-deficient deermice. Arch Biochem Biophys 303: 339–348, 1993PubMedCrossRefGoogle Scholar
  84. 84.
    Knecht KT, Adachi Y, Bradford BU, Iimuro Y, Kadiiska M, Xuang QH, Thurman RG: Free radical adducts in the bile of rats treated chronically with intragastric alcohol: Inhibition by destruction of Kupffer cells. Mol Pharmacol 47: 1028–1034, 1995PubMedGoogle Scholar
  85. 85.
    Thurman RG, Gao W, Connor HD, Adachi Y, Stachlewitz RF, Zhong Z, Knecht KT, Bradford BU, Mason RP, Lemasters JJ: Role of Kupffer cells in failure of fatty livers following liver transplantation and alcoholic liver injury. J Gastroenterol Hepatol 10: 524–530, 1995CrossRefGoogle Scholar
  86. 86.
    Moore DR, Reinke LA, McCay PB: Metabolism of ethanol to 1hydroxyethyl radicalsin vivo:Detection with intravenous administration of a-(4-pyridyl-1-oxide)-N-t-butylnitrone. Mol Pharmacol 47: 1224–1230, 1995PubMedGoogle Scholar
  87. 87.
    Ishii H, Kurose I, Kato S: Pathogenesis of alcoholic liver disease with particular emphasis on oxidative stress. J Gastroenterol Hepatol 12: 5272–5282, 1997CrossRefGoogle Scholar
  88. 88.
    Reinke LA, McCay PB: Spin trapping studies of alcohol-initiated radicals in rat liver: Influence of dietary fat. J Nutr 127: 8995–9025, 1997Google Scholar
  89. 89.
    Thurman RG, Bradford BU, Iimuro Y, Knecht KT, Arteel GE, Yin M, Connor HD, Wall C, Raleigh JA, Frankenberg MV, Adachi Y, Forman DT, Brenner D, Kadiiska M, Mason RP: The role of gut-derived bacterial toxins and free radicals in alcohol-induced liver injury. J Gastroenterol Hepatol 13: S39–S50, 1998Google Scholar
  90. 90.
    Thurman RG, Bradford BU, Iimuro Y, Frankenberg MV, Knecht KT, Connor HD, Adachi Y, Wall C, Arteel GE, Raleigh JA, Forman DT, Mason RP: Mechanisms of alcohol-induced hepatotoxicity: Studies in rats. Front Biosci 4: E42–E46, 1999PubMedCrossRefGoogle Scholar
  91. 91.
    Albano E, French SW, Ingelman-Sundberg M: Hydroxyethyl radicals in ethanol hepatotoxicity. Front Biosci 4: D533–D540, 1999PubMedCrossRefGoogle Scholar
  92. 92.
    Jokelainen K, Reinke LA, Nanji AA: Nf-kappab activation is associated with free radical generation and endotoxemia and precedes pathological liver injury in experimental alcoholic liver disease. Cytokine 16: 36–39, 2001PubMedCrossRefGoogle Scholar
  93. 93.
    Albano E, Cheeseman KH, Tomasi A, Carini R, Dianzani MU, Slater TF: Effect of spin traps in isolated rat hepatocytes and liver microsomes. Biochem Pharmacol 35: 3955–3960, 1986PubMedCrossRefGoogle Scholar
  94. 94.
    Niemela O, Klajner F, Orrego H, Vidins E, Blendis L, Israel Y: Antibodies against acetaldehyde-modified protein epitopes in human alcoholics. Hepatology 7: 1210–1214, 1987PubMedCrossRefGoogle Scholar
  95. 95.
    Fang JL, Vaca CE: Detection of DNA adducts of acetaldehyde in peripheral white blood cells of alcohol abusers. Carcinogenesis 18: 627–632, 1997PubMedCrossRefGoogle Scholar
  96. 96.
    Nakao LS, Kadiiska MB, Mason RP, Grijalba MT, Augusto O: Metabolism of acetaldehyde to methyl and acetyl radicals:In vitroandin vivoelectron paramagnetic resonance spin-trapping studies. Free Radie Biol Med 29: 721–729, 2000CrossRefGoogle Scholar
  97. 97.
    Kadiiska MB, Xiang QH, Mason RP:In vivofree radical generation by chromium(VI): An electron spin resonance spin-trapping investigation. Chem Res Toxicol 7: 800–805, 1994PubMedCrossRefGoogle Scholar
  98. 98.
    Kadiiska MB, Morrow JD, Awad JA, Roberts LJ II, Mason RP: Identification of free radical formation and F2-isoprostanesin vivoby acute Cr(VI) poisoning. Chem Res Toxicol 11: 1516–1520, 1998PubMedCrossRefGoogle Scholar
  99. 99.
    Kadiiska MB, Mason RP: Acute methanol intoxication generates free radicals in rats: An ESR spin trapping investigation. Free Radio Biol Med 28: 1106–1114, 2000CrossRefGoogle Scholar
  100. 100.
    Kadiiska MB, Mason RP: Ethylene glycol generates free radical metabolites in rats: An ESRin vivospin trapping investigation. Chem Res Toxicol 13: 1187–1191, 2000PubMedCrossRefGoogle Scholar
  101. 101.
    Kadiiska MB, De Costa KS, Mason RP, Mathews JM: Reduction of 1,3-diphenyl-l-triazene by rat hepatic microsomes, by cecal micro-flora, and in rats generates the phenyl radical metabolite: An ESR spin-trapping investigation. Chem Res Toxicol 13: 1082–1086, 2000PubMedCrossRefGoogle Scholar
  102. 102.
    Hix S, Kadiiska MB, Mason RP, Augusto O:In vivometabolism of tert-butyl hydroperoxide to methyl radicals. EPR spin trapping and DNA methylation studies. Chem Res Toxicol 13: 1056–1064, 2000PubMedCrossRefGoogle Scholar
  103. 103.
    DikalovaAE, Kadiiska MB, Mason RP: Anin vivoESR spin-trapping study: Free radical generation in rats from formate intoxication: Role of the Fenton reaction. Proc NatlAcad Sci USA 98: 13549–13553, 2001CrossRefGoogle Scholar
  104. 104.
    Lanigan S: Final report on the safety assessment of methyl alcohol. Int J Toxicol 20: 57–85, 2001PubMedGoogle Scholar
  105. 105.
    Johlin FC, Swain E, Smith C, Tephly TR: Studies on the mechanism of methanol poisoning: Purification and comparison of rat and human liver 10-formyltetrahydrofolate dehydrogenase. Mol Pharmacol 35: 745–750, 1989PubMedGoogle Scholar
  106. 106.
    Jacobsen D, McMartin KE: Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. Med Toxicol 1: 309–334, 1986PubMedGoogle Scholar
  107. 107.
    Skrzydlewska E, Farbiszewski R: Decreased antioxidant defense mechanisms in rat liver after methanol intoxication. Free Radic Res 27: 369–375, 1997PubMedCrossRefGoogle Scholar
  108. 108.
    Poyer JL, McCay PB, Lai EK, Janzen EG, Davis ER: Confirmation of assignment of the trichloromethyl radical spin adduct detected by spin trapping during13C-carbon tetrachloride metabolismin vitroandin vivo.Biochem Biophys Res Commun 94: 1154–1160, 1980PubMedCrossRefGoogle Scholar
  109. 109.
    Albano E, Lott KA, Slater TF, Stier A, Symons MC, Tomasi A: Spin-trapping studies on the free-radical products formed by metabolic activation of carbon tetrachloride in rat liver microsomal fractions isolated hepatocytes andin vivoin the rat. Biochem J 204: 593–603, 1982PubMedGoogle Scholar
  110. 110.
    McCay PB, Lai EK, Poyer JL, DuBose CM, Janzen EG: Oxygen-and carbon-centered free radical formation during carbon tetrachloride metabolism. Observation of lipid radicalsin vivoandin vitro.J Biol Chem 259: 2135–2143, 1984PubMedGoogle Scholar
  111. 111.
    Janzen EG, Towner RA, Haire DL: Detection of free radicals generated from thein vitrometabolism of carbon tetrachloride using improved ESR spin trapping techniques. Free Radic Res Commun 3: 357–364, 1987PubMedCrossRefGoogle Scholar
  112. 112.
    Janzen EG, Towner RA, Brauer M: Factors influencing the formation of the carbon dioxide radical anion (’CO2 -) spin adduct of PBN in the rat liver metabolism of halocarbons. Free Radic Res Commun 4: 359–369, 1988CrossRefGoogle Scholar
  113. 113.
    Connor HD, Lacagnin LB, Knecht KT, Thurman RG, Mason RP: Reaction of glutathione with a free radical metabolite of carbon tetrachloride. Mol Pharmacol 37: 443–451, 1990PubMedGoogle Scholar
  114. 114.
    Knecht KT, Mason RP:In vivoradical trapping and biliary secretion of radical adducts of carbon tetrachloride-derived free radical metabolites. Drug Metab Dispos 16: 813–817, 1988PubMedGoogle Scholar
  115. 115.
    Connor HD, Thurman RG, Galizi MD, Mason RP: The formation of a novel free radical metabolite from CC14in the perfused rat liver andin vivo.J Biol Chem 261: 4542–4548, 1986PubMedGoogle Scholar
  116. 116.
    Knecht KT, Mason RP: The detection of halocarbon-derived radical adducts in bile and liver of rats. Drug Metab Dispos 19: 325–331, 1991PubMedGoogle Scholar
  117. 117.
    Reinke LA, Towner RA, Janzen EG: Spin trapping of free radical metabolites of carbon tetrachloridein vitroandin vivo:Effect of acute ethanol administration. Toxicol Appl Pharmacol 112: 17–23, 1992PubMedCrossRefGoogle Scholar
  118. 118.
    Sentjurc M, Mason RP: Inhibition of radical adduct reduction and reoxidation of the corresponding hydroxylamines inin vivospin trapping of carbon tetrachloride-derived radicals. Free Radic Biol Med 13: 151–160, 1992PubMedCrossRefGoogle Scholar
  119. 119.
    Tanaka N, Tanaka K, Nagashima Y, Kondo M, Sekihara H: Nitric oxide increases hepatic arterial blood flow in rats with carbon tetrachloride-induced acute hepatic injury. Gastroenterology 117: 173–180, 1999PubMedCrossRefGoogle Scholar
  120. 120.
    Muriel P: Nitric oxide protection of rat liver from lipid peroxidation, collagen accumulation, and liver damage induced by carbon tetrachloride. Biochem Pharmacol 56: 773–779, 1998PubMedCrossRefGoogle Scholar
  121. 121.
    Abedinzadeh Z: Sulfur-centered reactive intermediates derived from the oxidation of sulfur compounds of biological interest. Can J Physiol Pharmacol 79: 166–170, 2001PubMedCrossRefGoogle Scholar
  122. 122.
    Maples KR, Jordan SJ, Mason RP:In vivorat hemoglobin thiyl free radical formation following administration of phenylhydrazine and hydrazine-based drugs. Drug Metab Dispos 16: 799–803, 1988PubMedGoogle Scholar
  123. 123.
    Maples KR, Jordan SJ, Mason RP:In vivorat hemoglobin thiyl free radical formation following phenylhydrazine administration. Mol Pharmacol 33: 344–350, 1988PubMedGoogle Scholar
  124. 124.
    Maples KR, Kennedy CH, Jordan SJ, Mason RP:In vivothiyl free radical formation from hemoglobin following administration of hydroperoxides. Arch Biochem Biophys 277: 402–409, 1990PubMedCrossRefGoogle Scholar
  125. 125.
    Maples KR, Eyer P, Mason RP: Aniline-, phenylhydroxylamine-, nitrosobenzene-, and nitrobenzene-induced hemoglobin thiyl free radical formationin vivoandin vitro.Mol Pharmacol 37: 311–318, 1990PubMedGoogle Scholar
  126. 126.
    Berliner LJ: In: Physica Medica, 1989, 5, pp 63–75Google Scholar
  127. 127.
    Berliner LJ: In: EPR Imaging and In Vivo ESR. CRC Press, Boca Raton, 0, 1991, pp 291–305Google Scholar
  128. 128.
    Berliner U, Fujii H: In-vivo spectroscopy. In: Biological Magnetic Resonance. Plenum, New York, 1992, 11, pp 307–319.Google Scholar
  129. 129.
    Jiang J, Liu KJ, Shi X, Swartz HM: Detection of short-lived free radicals by low frequency ESR spin trapping in whole living animals: Evidence of sulfur trioxide anion free radical generationin vivo.Arch Biochem Biophys 319: 570–573, 1995PubMedCrossRefGoogle Scholar
  130. 130.
    Huie RE, Neta P: Chemical behavior of sulfur trioxide and sulfur penta-oxide radical anion in aqueous solutions. J Phys Chem 88: 5665–5669, 1984CrossRefGoogle Scholar
  131. 131.
    Stanbury DM: Reduction potentials involving inorganic free radicals in aqueous solution. Adv Inorg Chem 33: 69–138, 1989CrossRefGoogle Scholar
  132. 132.
    Li J, Huang FL, Huang KP: Glutathiolation of proteins by glutathione disulfide-S-oxide derived from S-nitrosoglutathione. J Biol Chem 276: 3098–3105, 2000Google Scholar
  133. 133.
    Radi R, Beckman JS, Bush KM, Freeman BA: Peroxynitrite oxidation of sulthydryls. J Biol Chem 266: 4244–4250, 1991PubMedGoogle Scholar
  134. 134.
    Finley JW, Wheeler EL, Witt SC: Oxidation of glutathione by hydrogen peroxide and other oxidizing agents. J Agric Food Chem 29: 404–407, 1981PubMedCrossRefGoogle Scholar
  135. 135.
    Bonini MG, Augusto O: Carbon dioxide stimulates the production of thiyl, sulfinyl, and disulfide radical anion from thiol oxidation by peroxynitrite. J Biol Chem 276: 9749–9754, 2000PubMedCrossRefGoogle Scholar
  136. 136.
    Langley-Evans SC, Phillips GJ, Jackson AA: Sulphur dioxide: A potent glutathione depleting agent. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 114: 89–98, 1996PubMedCrossRefGoogle Scholar
  137. 137.
    Chamulitrat W: Desulfonation ofa colitis inducer 2,4,6-trinitrobenzene sulfonic acid produces sulfite radical. Biochim Biophys Acta 1472: 368–375, 1999PubMedCrossRefGoogle Scholar
  138. 138.
    Palmer RM, Ferrige AG, Moncada S: Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526, 1987PubMedCrossRefGoogle Scholar
  139. 139.
    Collier J, Vallance P: Second messenger role for NO widens to nervous and immune systems. Trends Pharmacol Sci 10: 427–431, 1989PubMedCrossRefGoogle Scholar
  140. 140.
    Shoji H, Takahashi S, Okabe E: Intracellular effects of nitric oxide on force production and Ca“ sensitivity of cardiac myofilaments. Antiox Redox Signal 1: 509–521, 1999CrossRefGoogle Scholar
  141. 141.
    Remer KA, Jungi TW, Fatzer R, Tauber MG, Leib SL: Nitric oxide is protective in listeric meningoencephalitis of rats. Infect Immun 69: 4086–4093, 2001PubMedCrossRefGoogle Scholar
  142. 142.
    Zweier JL, Fertmann J, Wei G: Nitric oxide and peroxynitrite in postischemic myocardium. Antiox Redox Signal 3: 11–22, 2001CrossRefGoogle Scholar
  143. 143.
    Archer S: Measurement of nitric oxide in biological models. FASEB J 7: 349–360, 1993PubMedGoogle Scholar
  144. 144.
    Michelakis ED, Archer SL: The measurement of NO in biological systems using chemiluminescence. Meth Mol Biol 100: 111–127, 1998Google Scholar
  145. 145.
    Ignarro LJ, Byrns RE, Buga GM, Wood KS: Endothelium-derived relaxing factor from pulmonary artery and vein possesses pharmacologic and chemical properties identical to those of nitric oxide radical. Circ Res 61: 866–879, 1987PubMedCrossRefGoogle Scholar
  146. 146.
    Ignarro LJ, Buga GM, Wood KS, Byrns RE, Chaudhuri G: Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84: 9265–9269, 1987CrossRefGoogle Scholar
  147. 147.
    Greenberg SS, Wilcox DE, Rubanyi GM: Endothelium-derived relaxing factor released from canine femoral artery by acetylcholine cannot be identified as free nitric oxide by electron paramagnetic resonance spectroscopy. Circ Res 67: 1446–1452, 1990PubMedCrossRefGoogle Scholar
  148. 148.
    Arroyo CM, Forray C: Activation of cyclic GMP formation in mouse neuroblastoma cells by a labile nitroxyl radical. An electron paramagnetic resonance/spin trapping study. Eur J Pharmaco1208: 157–161, 1991Google Scholar
  149. 149.
    Arroyo CM, Kohno M: Difficulties encountered in the detection of nitric oxide by spin trapping techniques. A cautionary note. Free Radic Res Commun 14: 145–155, 1991PubMedCrossRefGoogle Scholar
  150. 150.
    Mordvintcev P, Mulsch A, Busse R, Vanin A: On-line detection of nitric oxide formation in liquid aqueous phase by electron paramagnetic resonance spectroscopy. Anal Biochem 199: 142–146, 1991PubMedCrossRefGoogle Scholar
  151. 151.
    Akaike T, Yoshida M, Miyamoto Y, Sato K, Kohno M, Sasamoto K, Miyazaki K, Ueda S, Maeda H: Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor ‘NO through a radical reaction. Biochemistry 32: 827–832, 1993PubMedCrossRefGoogle Scholar
  152. 152.
    Komarov A, Mattson D, Jones MM, Singh PK, Lai CS:In vivospin trapping of nitric oxide in mice. Biochem Biophys Res Commun 195: 1191–1198, 1993PubMedCrossRefGoogle Scholar
  153. 153.
    Korth HG, Sustmann R, Thater C, Butler AR, Ingold KU: On the mechanism of the nitric oxide synthase-catalyzed conversion of Nomega-hydroxyl-L-arginine to citrulline and nitric oxide. J Biol Chem 269: 17776–17779, 1994PubMedGoogle Scholar
  154. 154.
    Woldman YYU, Khramtsov VV, Grigor’ev IA, Kiriljuk IA, Utepbergenov DI: Spin trapping of nitric oxide by nitronylnitroxides: Measurement of the activity of NO synthase from rat cerebellum. Biochem Biophys Res Commun 202: 195–203, 1994PubMedCrossRefGoogle Scholar
  155. 155.
    Obolenskaya MYu, Vanin AF, Mordvintcev PI, Mulsch A, Decker K: EPR evidence of nitric oxide production by the regenerating rat liver. Biochem Biophys Res Commun 202: 571–576, 1994PubMedCrossRefGoogle Scholar
  156. 156.
    Vanin AF, Huisman A, Stroes ES, de Ruijter-Heijstek FC, Rabelink TJ, van Faassen EE: Antioxidant capacity of mononitrosyl-irondithiocarbamate complexes: Implications for NO trapping. Free Radic Biol Med 30: 813–824, 2001PubMedCrossRefGoogle Scholar
  157. 157.
    Fujii S, Yoshimura T: Detection and imaging of endogenously produced nitric oxide with electron paramagnetic resonance spectroscopy. Antiox Redox Signal 2: 879–901, 2000CrossRefGoogle Scholar
  158. 158.
    Xia Y, Cardounel AJ, Vanin AF, Zweier JL: Electron paramagnetic resonance spectroscopy with N-methyl-D-glucamine dithiocarbamate iron complexes distinguishes nitric oxide and nitroxyl anion in a redox-dependent manner: Applications in identifying nitrogen monoxide products from nitric oxide synthase. Free Radic Biol Med 29: 793–797, 2000PubMedCrossRefGoogle Scholar
  159. 159.
    Kleschyov AL, Mollnau H, Oelze M, Meinertz T, Huang Y, Harrison DG, Munzel T: Spin trapping of vascular nitric oxide using colloid Fe(II)-diethyldithiocarbamate. Biochem Biophys Res Commun 275: 672–677, 2000PubMedCrossRefGoogle Scholar
  160. 160.
    Komarov AM, Mak IT, Weglicki WB: Iron potentiates nitric oxide scavenging by dithiocarbamates in tissue of septic shock mice. Biochim Biophys Acta 1361: 229–234, 1997PubMedCrossRefGoogle Scholar
  161. 161.
    Chamulitrat W: EPR studies of nitric oxide interactions of alkoxyl and peroxyl radicals inin vitroandex vivomodel systems. Antiox Redox Signal 3: 177–187, 2001CrossRefGoogle Scholar
  162. 162.
    Vladimirov Y, Borisenko G, Boriskina N, Kazarinov K, Osipov A: NO-hemoglobin may be a light-sensitive source of nitric oxide both in solution and in red blood cells. J Photochem Photobiol B 59: 115122, 2000Google Scholar
  163. 163.
    Weber H: Spin trapping in the determination of nitric oxide (NO). Pharm Unserer Zeit 28: 138–146, 1999PubMedCrossRefGoogle Scholar
  164. 164.
    Vanin AF: Iron diethyldithiocarbamate as spin trap for nitric oxide detection. Meth Enzymol 301: 269–279, 1999PubMedCrossRefGoogle Scholar
  165. 165.
    Galleano M, Aimo L, Virginia Borroni M, Puntarulo S: Nitric oxide and iron overload. Limitations of ESR detection by DETC. Toxicology 167: 199–205, 2001PubMedCrossRefGoogle Scholar
  166. 166.
    Tsuchiya K, Takasugi M, Minakuchi K, Fukuzawa K: Sensitive quantitation of nitric oxide by EPR spectroscopy. Free Radic Biol Med 21: 733–737, 1996PubMedCrossRefGoogle Scholar
  167. 167.
    Wallis G, Brackett D, Lerner M, Kotake Y, Bolli R, McCay PB:In vivospin trapping of nitric oxide generated in the small intestine, liver, and kidney during the development of endotoxemia: A time-course study. Shock 6: 274–278, 1996PubMedCrossRefGoogle Scholar
  168. 168.
    Kotake Y, Moore DR, Sang H, Reinke LA: Continuous monitoring ofin vivonitric oxide formation using EPR analysis in biliary flow. Nitric Oxide 3: 114–122, 1999PubMedCrossRefGoogle Scholar
  169. 169.
    Lai CS, Komarov AM: Spin trapping of nitric oxide producedin vivoin septic-shock mice. FEBS Lett 345: 120–124, 1994PubMedCrossRefGoogle Scholar
  170. 170.
    Fujii H, Koscielniak J, Berliner LJ: Determination and characterization of nitric oxide generation in mice byin vivoL-Band EPR spectroscopy. Mag Res Med 38: 565–568, 1997CrossRefGoogle Scholar
  171. 171.
    James PE, Miyake M, Swartz HM: Simultaneous measurement of NO’ and PO2from tissue byin vivoEPR. Nitric Oxide 3: 292–301, 1999PubMedCrossRefGoogle Scholar
  172. 172.
    Jackson SK, Madhani M, Thomas M, Timmins GS, James PE: Applications ofin vivoelectron paramagnetic resonance (EPR) spectroscopy: Measurements of p02and NO in endotoxin shock. Toxicol Lett 120: 253–257, 2001PubMedCrossRefGoogle Scholar
  173. 173.
    Swart HM, Baci G, Friedman B, God F, Grinberg OY, Hoopes PJ, Jiang J, Liu KJ, Nakashima T, O’Hara J, Walczak T: Measurement of p02 in vivo, including human subjects by electron paramagnetic resonance. Adv Exp Med Biol 361: 119–128, 1995CrossRefGoogle Scholar
  174. 174.
    Swartz HM, Dunn JF (eds): Measurements of Oxygen in Tissues: Overview and Perspectives on Methods to Make the Measurements. Oxygen Transport to Tissue XXII. Pabst Science Publishers, Lengerich, 2002Google Scholar
  175. 175.
    Swartz HM, Clarkson RB: The measurement of oxygenin vivousing EPR techniques. Phys Med Biol 43: 1957–1975, 1998PubMedCrossRefGoogle Scholar
  176. 176.
    Grucker D: Oxymetry by magnetic resonance: Applications to animal biology and medicine. Prog Nuclear Mag Res Spectroscopy 36: 241–270, 2000CrossRefGoogle Scholar
  177. 177.
    Goda F, O’Hara JA, Liu KJ, Rhodes ES, Dunn JF, Swartz HM: Comparisons of measurements of p02in tissuein vivoby EPR oximetry and microelectrodes. Adv Exp Med Biol 411: 543–549, 1997PubMedCrossRefGoogle Scholar
  178. 178.
    Lin JC, Song CW: Effects of hydralazine on the blood flow in RIF1 tumors and normal tissues of mice. Radiat Res 124: 171–177, 1990PubMedCrossRefGoogle Scholar
  179. 179.
    Bees PS, Sotak CH: Assessment of changes in murine tumor oxygenation in response to nicotinamide using1°F NMR relaxometry of a perfluorocarbon emulsion. Mag Res Med 29: 303–310, 1993CrossRefGoogle Scholar
  180. 180.
    Kim IH, Lemmon MJ, Brown JM: The influence of irradiation of the tumor bed on tumor hypoxia: Measurements by radiation response, oxygen electrodes, and nitroimidazole binding. Radiat Res 135: 411–417, 1993PubMedCrossRefGoogle Scholar
  181. 181.
    Horsman MR, Khalil AA, Siemann DW, Grau C, Hill SA, Lynch EM, Chaplin DJ, Overgaard J: Relationship between radiobiological hypoxia in tumors and electrode measurements of tumor oxygenation. Int J Radiat Oncol Biol Phys 29: 439–442, 1994PubMedCrossRefGoogle Scholar
  182. 182.
    Smirnov AI, Norby SW, Clarkson RB, Walczak T, Swartz HM: Simultaneous multi-site EPR spectroscopyin vivo.Mag Res Med 30: 213–220, 1993CrossRefGoogle Scholar
  183. 183.
    Grinberg OY, Smirnov AI, Swartz HM: High spatial resolution multi-site EPR oximetry. J Mag Res 152: 247–258, 2001Google Scholar
  184. 184.
    Swartz HM, Boyer S, Brown D, Chang K, Gast P, Glockner JF, Hu H, Liu KJ, Moussavi M, Nilges M: The use of EPR for the measurement of the concentration of oxygenin vivoin tissues under physiologically pertinent conditions and concentrations. Adv Exp Med Biol 317: 221–228, 1992PubMedCrossRefGoogle Scholar
  185. 185.
    Nakashima T, Goda F, Jiang J, Shima T, Swartz HM: Use of EPR oximetry with India ink to measure the pO2in the liverin vivoin mice. Mag Res Med 34: 888–892, 1995CrossRefGoogle Scholar
  186. 186.
    Jiang J, Nakashima T, Liu KJ, Goda F, Shima T, Swartz HM: Measurement of PO2in liver using EPR oximetry. J Appl Physiol 80: 552–558, 1996PubMedGoogle Scholar
  187. 187.
    James PE, Bacic G, Grinberg OY, Goda F, Dunn JF, Jackson SK, Swartz HM: Endotoxin-induced changes in intrarenal pO2measured byin vivo electron paramagnetic resonance oximetry and magnetic resonance imaging. Free Radic Biol Med 21: 25–34, 1996PubMedCrossRefGoogle Scholar
  188. 188.
    Chen K, Glockner JF, Morse PD 2nd, Swartz HM: Effects of oxygen on the metabolism of nitroxide spin labels in cells. Biochemistry 28: 2496–2501, 1989PubMedCrossRefGoogle Scholar
  189. 189.
    Kocherginsky N, Swartz HM: In: Nitroxide Spin Labels, Reactions in Biology and Chemistry. CRC Press, 1995Google Scholar
  190. 190.
    Fuchs J, Groth N, Herrling T, Zimmer G: Electron paramagnetic resonance studies on nitroxide radical2,2,5,5-tetramethyl-4-piperidin-loxyl (TEMPO) redox reactions in human skin. Free Radic Biol Med 22: 967–976, 1997Google Scholar
  191. 191.
    Yokoyama H, Lin Y, Itoh O, Ueda Y, Nakajima A, Ogata T, Sato T, Ohya-Nishiguchi H, Kamada H: EPR imaging forin vivoanalysis of the half-life of a nitroxide radical in the hippocampus and cerebral cortex of rats after epileptic seizures. Free Radic Biol Med 27: 442–448, 1999PubMedCrossRefGoogle Scholar
  192. 192.
    Yokoyama H, Itoh O, Ogata T, Obara H, Ohya-Nishiguchi H, Kamada H: Temporal brain imaging by a rapid scan ESR-CT system in rats receiving intraperitoneal injection of a methyl ester nitroxide radical. Mag Res Imaging 15: 1079–1084, 1997CrossRefGoogle Scholar
  193. 193.
    Yokoyama H, Itoh O, Aoyama M, Obara H, Ohya H, Kamada H:In vivoEPR imaging by using an acyl-protected hydroxylamine to analyze intracerebral oxidative stress in rats after epileptic seizures. Mag Res Imaging 18: 875–879, 2000CrossRefGoogle Scholar
  194. 194.
    Sano T, Umeda F, Hashimoto T, Nawata H, Utsumi H: Oxidative stress measurement byin vivoelectron spin resonance spectroscopy in rats with streptozotocin-induced diabetes. Diabetologia 41: 1355–1360, 1998PubMedCrossRefGoogle Scholar
  195. 195.
    Hockel M, Schlenger K, Mitze M, Schaffer U, Vaupel P: Hypoxia and radiation response in human tumors. Semin Radiat Oncol 6: 3–9, 1996PubMedCrossRefGoogle Scholar
  196. 196.
    Hockel M, Schienger K, Aral B, Mitze M, Schaffer U, Vaupel P: Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res 56: 4509–4515, 1996PubMedGoogle Scholar
  197. 197.
    Thews O, Vaupel P: Relevant parameters for describing the oxygenation status of solid tumors. Strahlenther Onkol 172: 239–243, 1996PubMedGoogle Scholar
  198. 198.
    James PE, O’Hara JA, Grinberg S, Panz T, Swartz HM: Impact of the antimetastatic drug Batimastat on tumor growth and PO2measured by EPR oximetry in a murine mammary adenocarcinoma. Adv Exp Med Biol 471: 487–496, 1999PubMedCrossRefGoogle Scholar
  199. 199.
    O’Hara JA, Goda F, Liu KJ, Bacic G, Hoopes PJ, Swartz HM: The pO2in a murine tumor after irradiation: Anin vivoelectron paramagnetic resonance oximetry study. Radiat Res 144: 222–229, 1995PubMedCrossRefGoogle Scholar
  200. 200.
    O’Hara JA, Goda F, Demidenko E, Swartz HM: Effect on regrowth delay in a murine tumor of scheduling split-dose irradiation based on direct pO2measurements by electron paramagnetic resonance oximetry. Radiat Res 150: 549–556, 1998PubMedCrossRefGoogle Scholar
  201. 201.
    O’Hara JA, Blumenthal RD, Grinberg OY, Demidenko E, Grinberg S, Wilmot CM, Taylor AM, Goldenberg DM, Swartz HM: Response to radioimmunotherapy correlates with tumor pO2measured by EPR oximetry in human tumor xenografts. Radiat Res 155: 466–473, 2001PubMedCrossRefGoogle Scholar
  202. 202.
    Chen K, Swartz HM: The products of the reduction of doxyl stearates in cells are hydroxylamines as shown by oxidation by15N-perdeuterated tempone. Biochim Biophys Acta 992: 131–133, 1989PubMedCrossRefGoogle Scholar
  203. 203.
    Swartz HM, Chen K, Pals M, Sentjurc M, Morse PD II: Hypoxiasensitive NMR contrast agents. Mag Res Med 3: 169–174, 1986CrossRefGoogle Scholar
  204. 204.
    Chen K, Lutz NW, Wehrle JP, Glickson JD, Swartz HM: Selective suppression of lipid resonance’s by lipid-soluble nitroxides in NMR spectroscopy. Mag Res Med 25: 120–127, 1992CrossRefGoogle Scholar
  205. 205.
    Miura Y, Anzai K, Urano S, Ozawa T:In vivoelectron paramagnetic resonance studies on oxidative stress caused by X-irradiation in whole mice. Free Radic Biol Med 23: 533–540, 1997PubMedCrossRefGoogle Scholar
  206. 206.
    Valgimigli L, Valgimigli M, Gaiani S, Pedulli GF, Bolondi L: Measurement of oxidative stress in human liver by EPR spin-probe technique. Free Radic Res 33: 167–178, 2000PubMedCrossRefGoogle Scholar
  207. 207.
    Miura Y, Ozawa T: Noninvasive study of radiation-induced oxidative damage usingin vivoelectron spin resonance. Free Radic Biol Med 28: 854–859, 2000PubMedCrossRefGoogle Scholar
  208. 208.
    Packer L: Biothiols. Meth Enzymol 251: 529, 1995Google Scholar
  209. 209.
    Boyne AF, Ellman GL: Amethodology for analysis of tissue sulfhydryl components. Anal Biochem 46: 639–653, 1972PubMedCrossRefGoogle Scholar
  210. 210.
    Kosower EM, Kosower NS: Bromobimane probes for thiols. Meth Enzymol 251: 133–148, 1995PubMedCrossRefGoogle Scholar
  211. 211.
    Rabenstein DL, Arnold AP, Guy RD: ‘H-NMR study of the removal of methylmercury from intact erythrocytes by sulthydryl compounds. J Inorg Biochem 28: 279–287, 1986PubMedCrossRefGoogle Scholar
  212. 212.
    Khramtsov VV, Yelinova VI, Weiner LM, Berezina TA, Martin VV, Volodarsky LB: Quantitative determination of SH groups in low-and high-molecular weight compounds by an electron spin resonance method. Anal Biochem 182: 58–663, 1989PubMedCrossRefGoogle Scholar
  213. 213.
    Weiner LM: Quantitative determination of thiol groups in low and high molecular weight compounds by electron paramagnetic resonance. Meth Enzymol 251: 87–105, 1995PubMedCrossRefGoogle Scholar
  214. 214.
    Weiner LM, Hu H, Swartz HM: EPR method for the measurement of cellular sulfhydryl groups. FEBS Lett 290: 243–246, 1991PubMedCrossRefGoogle Scholar
  215. 215.
    Busse E, Zimmer G, Schopohl B, Kornhuber B: Influence of a-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittelforschung 42: 829–831, 1992PubMedGoogle Scholar
  216. 216.
    Busse E, Zimmer G, Komhuber B: Intracellular changes of HeLa cells after single or repeated treatment with cytostatics. Arzneimittelforschung 43: 378–381, 1993PubMedGoogle Scholar
  217. 217.
    Dikalov S, Kirilyuk I, Grigor’ev I: Spin trapping of O-, C-, and S-centered radicals and peroxynitrite by2H-imidazole-l -oxides. Biochem Biophys Res Commun 218: 616–622, 1996PubMedCrossRefGoogle Scholar
  218. 218.
    Dikalov S, Khramtsov V, Zimmer G: Determination of rate constants of the reactions of thiols with superoxide radical by electron paramagnetic resonance: Critical remarks on spectrophotometric approaches. Arch Biochem Biophys 326: 207–218, 1996PubMedCrossRefGoogle Scholar
  219. 219.
    Nohl H, Stolze K, Weiner LM: Noninvasive measurement of thiol levels in cells and isolated organs. Meth Enzymol 251: 191–203, 1995PubMedCrossRefGoogle Scholar
  220. 220.
    Yelinova V, Glazachev Y, Khramtsov V, Kudryashova L, Rykova V, Salganik R: Studies of human and rat blood under oxidative stress: Changes in plasma thiol level, antioxidant enzyme activity, protein carbonyl content, and fluidity of erythrocyte membrane. Biochem Biophys Res Commun 221: 300–303, 1996PubMedCrossRefGoogle Scholar
  221. 221.
    Khramtsov VV, Elinova VI, Goriunova TE, Vainer LM: Quantitative determination and reversible modification of sulfhydryl groups in low and high molecular weight compounds using a biradical spin marker. Biokhimiia 56: 1567–1577, 1991PubMedGoogle Scholar
  222. 222.
    Yelinova VI, Weiner LM, Slepneva IA, Levina AS: Reversible modification of cysteine residues of NADPH-cytochrome P-450 reductase. Biochem Biophys Res Commun 193: 1044–1048, 1993PubMedCrossRefGoogle Scholar
  223. 223.
    Khramtsov VV, Yelinova VI, Glazachev YuI, Reznikov VA, Zimmer G: Quantitative determination and reversible modification of thiols using imidazolidine biradical disulfide label. J Biochem Biophys Meth 35: 115–128, 1997PubMedCrossRefGoogle Scholar
  224. 224.
    Galster H: pH Measurements: Fundamentals, Methods, Applications, Instrumentation. VCH, Weinhein, 1991Google Scholar
  225. 225.
    Mignano AG, Baldini F: Biomedical sensors using optical fibres. Rep Prog Phys 59:1–28, 1996CrossRefGoogle Scholar
  226. 226.
    Runnels PL, Joseph JD, Logman MJ, Wightman RM: Effect of pH and surface functionality’s on the cyclic voltammetric responses of carbon-fiber microelectrodes. Anal Chem 71: 2782–2789, 1999PubMedCrossRefGoogle Scholar
  227. 227.
    Willoughby D, Thomas RC, Schwiening CJ: A role for Na’/H’ exchange in pH regulation in helix neurones. Pflügers Arch 438: 741–749, 1999CrossRefGoogle Scholar
  228. 228.
    Kotyk JJ, Rust RS, Ackerman JJ, Deuel RK: Simultaneousin vivomonitoring of cerebral deoxyglucose and deoxyglucose-6-phosphate by13C[1H] nuclear magnetic resonances spectroscopy. J Neurochem 53: 1620–1628, 1989PubMedCrossRefGoogle Scholar
  229. 229.
    Zhou HZ, Malhotra D, Doers J, Shapiro JI: Hypoxia and metabolic acidosis in the isolated heart: Evidence for synergistic injury. Mag Res Med 29: 94–98, 1993CrossRefGoogle Scholar
  230. 230.
    Braun FJ, Hegemann P: Direct measurement of cytosolic calcium and pH in livingChlamydomonas reinhardtiicells. Eur J Cell Biol 78: 199–208, 1999PubMedCrossRefGoogle Scholar
  231. 231.
    Manning TJ Jr, Sontheimer H: Recording of intracellular Ca2’, Cl-pH and membrane potential in cultured astrocytes using a fluorescence plate reader. J Neurosci Meth 91: 73–81, 1999CrossRefGoogle Scholar
  232. 232.
    Khramtsov VV, Marsh D, Weiner L, Grigoriev IA, Volodarsky LB: Proton exchange in stable nitroxyl radicals. EPR study of the pH of aqueous solutions. Chem Phys Lett 91: 69–72, 1982CrossRefGoogle Scholar
  233. 233.
    Khramtsov VV, Weiner LM: In: Proton Exchange in Stable Nitroxyl Radicals: pH-Sensitive Spin Probes, Imidazoline Nitroxides, vol. II. CRC press, Boca Raton, FL, 1988, pp 37–80Google Scholar
  234. 234.
    Khramtsov VV, Marsh D, Weiner L, Reznikov VA: The application of pH-sensitive spin labels to studies of surface potential and polarity of phospholipid membranes and proteins. Biochim Biophys Acta 1104: 317–324, 1992PubMedCrossRefGoogle Scholar
  235. 235.
    Kroll C, Mader K, Stober R., Borchert HH: Direct and continuous determination of pH values in nontransparent w/o systems by means of EPR spectroscopy. Eur J Pharmaceut Sci 3: 21–26, 1995CrossRefGoogle Scholar
  236. 236.
    Gallez B, Mader K, Swartz HM: Noninvasive measurement of the pH inside the gut by using pH-sensitive nitroxides. Anin vivoEPR study. Mag Res Med 36: 694–697, 1996.CrossRefGoogle Scholar
  237. 237.
    Sotgiu A, Mader K, Placidi G, Colacicchi S, Ursini CL, Alecci M: pH-sensitive imaging by low-frequency EPR: A model study for biological applications. Phys Med Biol 43: 1921–1930, 1998PubMedCrossRefGoogle Scholar
  238. 238.
    Khramtsov VV, Grigor’ev IA, Foster MA, Lurie DJ, Nicholson I: Biological applications of spin pH probes. Cell Mol Biol (Noisy-legrand) 46: 1361–1374, 2000Google Scholar
  239. 239.
    Nicholson I, Robb FJL, Lurie DJ: Imaging paramagnetic species using radiofrequency longitudinally detected ESR. J Mag Res Series B 104: 284–288, 1994CrossRefGoogle Scholar
  240. 240.
    Lurie DJ, Nicholson I, Mallard JR: Low Field EPR measurements by field-cycled dynamic nuclear polarization. J Mag Res 95: 405–409,1991Google Scholar
  241. 241.
    Foster MA, Seimenis I, Lurie DJ: The application of PEDRI to the study of free radicalsin vivo.Phys Med Biol 43: 1893–1897, 1998PubMedCrossRefGoogle Scholar
  242. 242.
    Lurie DJ: Proton-electron double-resonance imaging (PEDRI). In: Biological Magnetic Resonance. Plenum, New York, 2000Google Scholar
  243. 243.
    Gallez B, Bacic G, Goda F, Jiang J, O’Hara JA, Dunn JF, Swartz HM: Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues:In vivoEPR and MRI studies. Mag Res Med 35: 97–106, 1996CrossRefGoogle Scholar
  244. 244.
    Cornett CR, Markesbery WR, Ehmann WD: Imbalances of trace elements related to oxidative damage in Alzheimer’s disease brain. Neurotoxicology 19: 339–345, 1998PubMedGoogle Scholar
  245. 245.
    Hirsch EC, Faucheux BA: Iron metabolism and Parkinson’s disease. Mov Disord 13: 39–45, 1998PubMedCrossRefGoogle Scholar
  246. 246.
    Mertz W, Roginski EE, Reba RC: Biological activity and fate of trace quantities of intravenous chromium(III) in the rat. Am J Physiol 209: 489–494, 1965PubMedGoogle Scholar
  247. 247.
    Laborda R, Diaz-Mayans J, Nunez A: Nephrotoxic and hepatotoxic effects of chromium compounds in rats. Bull Environ Contam Toxicol 36: 332–336, 1986PubMedCrossRefGoogle Scholar
  248. 248.
    Hojo Y, SatomiY: In vivonephrotoxicity induced in mice by chromium(VI). Involvement of glutathione and chromium(V). Biol Trace Elem Res 31: 21–31, 1991PubMedCrossRefGoogle Scholar
  249. 249.
    Ottenwaelder H, Wiegand HJ, Bolt HM: Uptake of51Cr(VI) by human erythrocytes: Evidence for a carrier-mediated transport mechanism. Sci Total Environ 71: 561–566, 1988PubMedCrossRefGoogle Scholar
  250. 250.
    Kitagawa S, Seki H, Kametani F, Sakurai H: Uptake of hexavalent chromium by bovine erythrocytes and its interaction with cytoplasmic components; the role of glutathione. Chem Biol Interact 40: 265–274, 1982PubMedCrossRefGoogle Scholar
  251. 251.
    Wiegand HJ, Ottenwalder H, Bolt HM: The reduction of chromium(VI) to chromium(III) by glutathione: An intracellular redox pathway in the metabolism of the carcinogen chromate. Toxicology 33: 341–348, 1984PubMedCrossRefGoogle Scholar
  252. 252.
    Goodgame DM, Joy AM: Relatively long-lived chromium(V) species are produced by the action of glutathione on carcinogenic chromium(VI). J Inorg Biochem 26: 219–224, 1986PubMedCrossRefGoogle Scholar
  253. 253.
    Shi XL, Dalai NS: On the mechanism of the chromate reduction by glutathione: ESR evidence for the glutathionyl radical and an isolable Cr(V) intermediate. Biochem Biophys Res Commun 156: 137–142, 1988PubMedCrossRefGoogle Scholar
  254. 254.
    Borges KM, Boswell JS, Liebross RH, Wetterhahn KE: Activation of chromium(VI) by thiols results in chromium(V) formation, chromium binding to DNA and altered DNA conformation. Carcinogenesis 12: 551–561, 1991PubMedCrossRefGoogle Scholar
  255. 255.
    Shi X, Rojanasakul Y, Gannett P, Liu K, Mao Y, Daniel LN, Ahmed N, Saffiotti U: Generation of thiyl and ascorbyl radicals in the reaction of peroxynitrite with thiols and ascorbate at physiological pH. J Inorg Biochem 56: 77–86, 1994PubMedCrossRefGoogle Scholar
  256. 256.
    Kawanishi S, Inoue S, Sano S: Mechanism of DNA cleavage induced by sodium chromate(VI) in the presence of hydrogen peroxide. J Biol Chem 261: 5952–5958, 1986PubMedGoogle Scholar
  257. 257.
    Steams DM, Courtney KD, Giangrande PH, Phieffer LS, Wetterhahn KE: Chromium(VI) reduction by ascorbate: Role of reactive intermediates in DNA damagein vitro.Environ Health Perspect 102: 21–25, 1994Google Scholar
  258. 258.
    Stearns DM, Wetterhahn KE: Reaction of chromium(VI) with ascorbate produces chromium(V), chromium(IV), and carbon-based radicals. Chem Res Toxicol 7: 219–230, 1994PubMedCrossRefGoogle Scholar
  259. 259.
    Sugiyama M, Ando A, Nakao K, Ueta H, Hidaka T, Ogura R: Influence of vitamin B2 on formation of chromium(V), alkali-labile sites, and lethality of sodium chromate(VI) in Chinese hamster V-79 cells. Cancer Res 49: 6180–6184, 1989PubMedGoogle Scholar
  260. 260.
    Shi XL, Dalai NS: Chromium(V) and hydroxyl radical formation during the glutathione reductase-catalyzed reduction of chromium(VI). Biochem Biophys Res Commun 163: 627–634, 1989PubMedCrossRefGoogle Scholar
  261. 261.
    Shi XL, Dalai NS: One-electron reduction of chromate by NADPHdependent glutathione reductase. J Inorg Biochem 40: 1–12, 1990PubMedCrossRefGoogle Scholar
  262. 262.
    Liu KJ, Jiang J, Swartz HM, Shi X: Low-frequency EPR detection of chromium(V) formation by chromium(VI) reduction in whole live mice. Arch Biochem Biophys 313: 248–252, 1994PubMedCrossRefGoogle Scholar
  263. 263.
    Baranowska-Dutkiewicz B: Absorption of hexavalent chromium by skin in man. Arch Toxicol 47: 47–50, 1981PubMedGoogle Scholar
  264. 264.
    Liu KJ, Mader K, Shi X, Swartz HM: Reduction of carcinogenic chromium(VI) on the skin of living rats. Mag Res Med 38: 524–526, 1997CrossRefGoogle Scholar
  265. 265.
    Sakurai H, Takechi K, Tsuboi H, Yasui H: ESR characterization and metallokinetic analysis of Cr(V) in the blood of rats given carcinogen chromate(VI) compounds. J Inorg Biochem 76: 71–80, 1999PubMedCrossRefGoogle Scholar
  266. 266.
    Dillard CJ, Tappel AL: Lipid peroxidation and copper toxicity in rats. Drug Chem Toxicol 7: 477–487, 1984PubMedCrossRefGoogle Scholar
  267. 267.
    Hasan M, Ali SF: Effects of thallium, nickel, and cobalt administration of the lipid peroxidation in different regions of the rat brain. Toxicol Appl Pharmacol 57: 8–13, 1981PubMedCrossRefGoogle Scholar
  268. 268.
    Yonaha M, Ohbayashi Y, Noto N, Itoh E, Uchiyama M: Effects of trivalent and hexavalent chromium on lipid peroxidation in rat liver microsomes. Chem Pharm Bull (Tokyo) 28: 893–899, 1980CrossRefGoogle Scholar
  269. 269.
    Susa N, Ueno S, Furukawa Y, Michiba N, Minoura S: Induction of lipid peroxidation in mice by hexavalent chromium and its relation to the toxicity. Nippon Juigaku Zasshi 51: 1103–1110, 1989PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Nadeem Khan
    • 1
  • Harold Swartz
    • 1
  1. 1.EPR Center, Department of Diagnostic RadiologyDartmouth Medical SchoolHanoverUSA

Personalised recommendations