Journal of Fluorescence

, Volume 16, Issue 1, pp 119–139 | Cite as

Use of Fluorescence Probes for Detection of Reactive Nitrogen Species: A Review

  • Ana Gomes
  • Eduarda Fernandes
  • José L. F. C. Lima
Original Article

The biological and toxicological effects that have been attributed to reactive nitrogen species (RNS) are increasingly stirring the scientific inquisitiveness about the molecular mechanisms involved. However, RNS present some characteristics that complicate their detection, namely their short lifetime and the normal presence of a variety of endogenous compounds capable of reacting with these reactive species, when the studies are performed in biological matrices. The development of methodologies capable of circumvent these difficulties is thus of fundamental importance. Fluorescence probes are particularly important due to their high sensibility and usefulness in temporal and spatial monitoring of RNS, particularly in microanalysis conditions in biological media akin to cells or tissues. In the present review is given an account of the fluorescence probes that have been used for detection of nitric oxide (NO), peroxynitrite anion (ONOO), as well as of some of its derivatives in biological and nonbiological media.


Reactive nitrogen species nitric oxide peroxynitrite fluorescence probes antioxidant oxidative stress scavenging activity free radicals 



The authors greatly acknowledge FCT and FEDER financial support for the project POCTI/QUI/59284/2004.


  1. 1.
    M. P. Fink (2002). Role of reactive oxygen species in acute respiratory distress syndrome. Curr. Opin. Crit. Care 8, 6–11.CrossRefPubMedGoogle Scholar
  2. 2.
    T. P. A. Devasagayam, J. C. Tilak, K. K. Boloor, K. S. Sane, S. S. Ghaskadbi, and R. D. Lele (2004). Free radicals and antioxidants in human health: Current status and future prospects. J. Assoc. Phys. India 52, 794–804.Google Scholar
  3. 3.
    M. P. Murphy, M. A. Packer, J. L. Scarlett, and S. W. Martin (1998). Peroxynitrite: A biologically significant oxidant. Gen. Pharmacol. 31, 179–186.CrossRefPubMedGoogle Scholar
  4. 4.
    O. von Bohlen und Halbach (2003). Nitric oxide imaging in living neuronal tissues using fluorescent probes. Nitric Oxide 9, 217–228.CrossRefPubMedGoogle Scholar
  5. 5.
    P. C. Dedon and S. R. Tannenbaum (2004). Reactive nitrogen species in the chemical biology of inflammation. Arch. Biochem. Biophys. 423, 12–22.CrossRefPubMedGoogle Scholar
  6. 6.
    S. Moncada, R. M. J. Palmer, and E. A. Higgs (1991). Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 43, 109–142.PubMedGoogle Scholar
  7. 7.
    H. J. Forman, J. M. Fukuto, and M. Torres (2004). Redox signaling: Thiol chemistry defines which reactive oxygen and nitrogen species can act as second messengers. Am. J. Physiol. Cell Physiol. 287, C246–C256.CrossRefPubMedGoogle Scholar
  8. 8.
    P. Kostka (1995). Free radicals (nitric oxide). Anal. Chem. 67, 411R–416R.CrossRefPubMedGoogle Scholar
  9. 9.
    L. J. Hofseth, S. P. Hussain, G. N. Wogan, and C. C. Harris (2003). Nitric oxide in cancer and chemoprevention. Free Radic. Biol. Med. 34, 955–968.CrossRefPubMedGoogle Scholar
  10. 10.
    A. K. Nussler and T. R. Billiar (1993). Inflammation, immunoregulation, and inducible nitric oxide synthase. J. Leukoc. Biol. 54, 171–178.PubMedGoogle Scholar
  11. 11.
    N. Miyasaka and Y. Hirata (1997). Nitric oxide and inflammatory arthritides. Life Sci. 61, 2073–2081.CrossRefPubMedGoogle Scholar
  12. 12.
    T. Esch, G. B. Stefano, G. L. Fricchione, and H. Benson (2002). Stress-related diseases—A potential role for nitric oxide. Med. Sci. Monit. 8, RA103–RA118.PubMedGoogle Scholar
  13. 13.
    R. E. Huie and S. Padmaja (1993). The reaction of NO with superoxide. Free Radic. Res. Commun. 18, 195–199.PubMedCrossRefGoogle Scholar
  14. 14.
    S. Goldstein and G. Czapski (1995). The reaction of NO with O2 ⋅− and HO2 : A pulse radiolysis study. Free Radic. Biol. Med. 19, 505–510.CrossRefPubMedGoogle Scholar
  15. 15.
    R. Kissner, T. Nauser, P. Bugnon, P. G. Lye, and W. H. Koppenol (1997). Formation and properties of peroxynitrite as studied by laser flash photolysis, high-pressure stopped-flow technique, and pulse radiolysis. Chem. Res. Toxicol. 10, 1285–1292.CrossRefPubMedGoogle Scholar
  16. 16.
    R. Radi, A. Cassina, R. Hodara, C. Quijano, and L. Castro (2002). Peroxynitrite reactions and formation in mitochondria. Free Radic. Biol. Med. 33, 1451–1464.CrossRefPubMedGoogle Scholar
  17. 17.
    B. Alvarez and R. Radi (2003). Peroxynitrite reactivity with amino acids and proteins. Amino Acids 25, 295–311.CrossRefPubMedGoogle Scholar
  18. 18.
    A. Denicola, J. M. Souza, and R. Radi (1998). Diffusion of peroxynitrite across erythrocyte membranes. Proc. Natl. Acad. Sci. U.S.A. 95, 3566–3571.CrossRefPubMedGoogle Scholar
  19. 19.
    U. Ketsawatsakul, M. Whiteman, and B. Halliwell (2000). A reevaluation of peroxynitrite scavenging activity of some dietary phenolics. Biochem. Biophys. Res. Commun. 279, 692–699.CrossRefPubMedGoogle Scholar
  20. 20.
    J. W. Coddington, J. K. Hurst, and S. V. Lymar (1999). Hydroxyl radical formation during peroxynitrous acid decomposition. J. Am. Chem. Soc. 121, 2438–2443.CrossRefGoogle Scholar
  21. 21.
    J. S. Beckman, T. W. Beckman, J. Chen, P. A. Marshall, and B. A. Freeman (1990). Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. U.S.A. 87, 1620–1624.PubMedGoogle Scholar
  22. 22.
    O. Augusto, R. M. Gatti, and R. Radi (1994). Spin-trapping studies of peroxynitrite decomposition and of 3-morpholinosydnonimine N-ethylcarbamide autooxidation: Direct evidence for metal-independent formation of free radical intermediates. Arch. Biochem. Biophys. 310, 118–125.CrossRefPubMedGoogle Scholar
  23. 23.
    R. Radi, T. P. Cosgrove, J. S. Beckman, and B. A. Freeman (1993). Peroxynitrite-induced luminol chemiluminescence. Biochem. J. 290, 51–57.PubMedGoogle Scholar
  24. 24.
    S. V. Lymar and J. K. Hurst (1995). Rapid reaction between peroxynitrite ion and carbon dioxide: Implications for biological activity. J. Am. Chem. Soc. 117, 8867–8868.CrossRefGoogle Scholar
  25. 25.
    M. G. Espey, K. M. Miranda, D. D. Thomas, S. Xavier, D. Citrin, M. P. Vitek, and D. A. Wink (2002). A chemical perspective on the interplay between NO, reactive oxygen species, and reactive nitrogen oxide species. Ann. N. Y. Acad. Sci. 962, 195–206.PubMedGoogle Scholar
  26. 26.
    S. L. Kohnen, A. A. Mouithys-Mickalad, G. P. Deby-Dupont, C. M. Deby, P. Hans, M. L. Lamy, and A. F. Noels (2003). Investigation of the reaction of peroxynitrite with propofol at acid pH: Predominant production of oxidized, nitrated, and halogenated derivatives. Nitric Oxide 8, 170–181.CrossRefPubMedGoogle Scholar
  27. 27.
    G. L. Squadrito and W. A. Pryor (1998). Oxidative chemistry of nitric oxide: The roles of superoxide, peroxynitrite, and carbon dioxide. Free Radic. Biol. Med. 25, 392–403.CrossRefPubMedGoogle Scholar
  28. 28.
    D. Jourd'heuil, K. M. Miranda, S. M. Kim, M. G. Espey, Y. Vodovotz, S. Laroux, C. T. Mai, A. M. Miles, M. B. Grisham, and D. A. Wink (1999). The oxidative and nitrosative chemistry of the nitric oxide/superoxide reaction in the presence of bicarbonate. Arch. Biochem. Biophys. 365, 92–100.CrossRefPubMedGoogle Scholar
  29. 29.
    A. Denicola, B. A. Freeman, M. Trujillo, and R. Radi (1996). Peroxynitrite reaction with carbon dioxide/bicarbonate: Kinetics and influence on peroxynitrite-mediated oxidations. Arch. Biochem. Biophys. 333, 49–58.CrossRefPubMedGoogle Scholar
  30. 30.
    R. Radi, J. S. Beckman, K. M. Bush, and B. A. Freeman (1991). Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide. Arch. Biochem. Biophys. 288, 481–487.CrossRefPubMedGoogle Scholar
  31. 31.
    R. Radi, J. S. Beckman, K. M. Bush, and B. A. Freeman (1991). Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide. J. Biol. Chem. 266, 4244–4250.PubMedGoogle Scholar
  32. 32.
    A. Van der Vliet, D. Smith, C. A. O'Neill, H. Kaur, V. Darley-Usmar, C. E. Cross, and B. Halliwell (1994). Interactions of peroxynitrite with human plasma and its constituents: Oxidative damage and antioxidant depletion. Biochem. J. 303, 295–301.PubMedGoogle Scholar
  33. 33.
    H. Ischiropoulos and A. B. Al-Mehdi (1995). Peroxynitrite-mediated oxidative protein modifications. FEBS Lett. 364, 279–282.CrossRefPubMedGoogle Scholar
  34. 34.
    V. Yermilov, Y. Yoshie, J. Rubio, and H. Ohshima (1996). Effects of carbon dioxide/bicarbonate on induction of DNA single-strand breaks and formation of 8-nitroguanine, 8-oxoguanine and base-propenal mediated by peroxynitrite. FEBS Lett. 399, 67–70.CrossRefPubMedGoogle Scholar
  35. 35.
    J. P. Spencer, J. Wong, A. Jenner, O. I. Aruoma, C. E. Cross, and B. Halliwell (1996). Base modification and strand breakage in isolated calf thymus DNA and in DNA from human skin epidermal keratinocytes exposed to peroxynitrite or 3-morpholinosydnonimine. Chem. Res. Toxicol. 9, 1152–1158.CrossRefPubMedGoogle Scholar
  36. 36.
    K. Kikugawa, K. Hiramoto, S. Tomiyama, and Y. Asano (1997). β-Carotene effectively scavenges toxic nitrogen oxide: Nitrogen dioxide and peroxynitrous acid. FEBS Lett. 404, 175–178.CrossRefPubMedGoogle Scholar
  37. 37.
    W. A. Pryor and G. L. Squadrito (1995). The chemistry of peroxynitrite: A product from the reaction of nitric oxide with superoxide. Am. J. Physiol. 268, L699–L722.PubMedGoogle Scholar
  38. 38.
    M. Kirsch and H. de Groot (1999). Reaction of peroxynitrite with reduced nicotinamide nucleotides, the formation of hydrogen peroxide. J. Biol. Chem. 274, 24664–24670.CrossRefPubMedGoogle Scholar
  39. 39.
    M. Kirsch and H. de Groot (2000). Ascorbate is a potent antioxidant against peroxynitrite-induced oxidation reactions. J. Biol. Chem. 275, 16702–16708.CrossRefPubMedGoogle Scholar
  40. 40.
    W. A. Pryor, X. Jin, and G. L. Squadrito (1994). One- and two-electron oxidations of methionine by peroxynitrite. Proc. Natl. Acad. Sci. U.S.A. 91, 11173–11177.PubMedGoogle Scholar
  41. 41.
    J. J. Moreno and W. A. Pryor (1992). Inactivation of α1-proteinase inhibitor by peroxynitrite. Chem. Res. Toxicol. 5, 425–431.CrossRefPubMedGoogle Scholar
  42. 42.
    B. Halliwell, K. Zhao, and M. Whiteman (1999). Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good. A personal view of recent controversies. Free Radic. Res. 31, 651–669.PubMedGoogle Scholar
  43. 43.
    S. B. Digerness, K. D. Harris, J. W. Kirklin, F. Urthaler, L. Viera, J. S. Beckman, and V. Darley-Usmar (1999). Peroxynitrite irreversibly decreases diastolic and systolic function in cardiac muscle. Free Radic. Biol. Med. 27, 1386–1392.CrossRefPubMedGoogle Scholar
  44. 44.
    S. K. Wattanapitayakul, D. M. Weinstein, B. J. Holycross, and J. A. Bauer (2000). Endothelial dysfunction and peroxynitrite formation are early events in angiotensin-induced cardiovascular disorders. FASEB J. 14, 271–278.PubMedGoogle Scholar
  45. 45.
    S. G. Hashjin, G. Folkerts, P. A. Henricks, R. B. Muijsers, and F. P. Nijkamp (1998). Peroxynitrite in airway diseases. Clin. Exp. Allergy 28, 1464–1473.CrossRefPubMedGoogle Scholar
  46. 46.
    J. S. Beckman (1996). Oxidative damage and tyrosine nitration from peroxynitrite. Chem. Res. Toxicol. 9, 836–844.CrossRefPubMedGoogle Scholar
  47. 47.
    A. G. Estévez, J. P. Crow, J. B. Sampson, C. Reiter, Y. Zhuang, G. J. Richardson, M. M. Tarpey, L. Barbeito, and J. S. Beckman (1999). Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science 286, 2498–2500.CrossRefPubMedGoogle Scholar
  48. 48.
    N. Soh, Y. Katayama, and M. Maeda (2001). A fluorescent probe for monitoring nitric oxide production using a novel detection concept. Analyst 126, 564–566.CrossRefPubMedGoogle Scholar
  49. 49.
    K. Tanaka, T. Miura, N. Umezawa, Y. Urano, K. Kikuchi, T. Higuchi, and T. Nagano (2001). Rational design of fluorescein-based fluorescence probes. Mechanism-based design of a maximum fluorescence probe for singlet oxygen. J. Am. Med. Soc. 123, 2530–2536.CrossRefGoogle Scholar
  50. 50.
    T. Nagano (1999). Practical methods for detection of nitric oxide. Luminescence 14, 283–290.CrossRefPubMedGoogle Scholar
  51. 51.
    M. M. Tarpey, D. A. Wink, and M. B. Grisham (2004). Methods for detection of reactive metabolites of oxygen and nitrogen: In vitro and in vivo considerations. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R431–R444.PubMedGoogle Scholar
  52. 52.
    T. P. Misko, R. J. Schilling, D. Salvemini, W. M. Moore, and M. G. Currie (1993). A fluorometric assay for the measurement of nitrite in biological samples. Anal. Biochem. 214, 11–16.CrossRefPubMedGoogle Scholar
  53. 53.
    N. Nakatsubo, H. Kojima, K. Sakurai, K. Kikuchi, H. Nagoshi, Y. Hirata, T. Akaike, H. Maeda, Y. Urano, T. Higuchi, and T. Nagano (1998). Improved nitric oxide detection using 2,3-diaminonaphthalene and its application to the evaluation of novel nitric oxide synthase inhibitors. Biol. Pharm. Bull. 21, 1247–1250.PubMedGoogle Scholar
  54. 54.
    L. Gonzalez-Santiago, S. Lopez-Ongil, M. Rodriguez-Puyol, and D. Rodriguez-Puyol (2002). Decreased nitric oxide synthesis in human endothelial cells cultured on type I collagen. Circ. Res. 90, 539–545.CrossRefPubMedGoogle Scholar
  55. 55.
    D. J. Kleinhenz, X. Fan, J. Rubin, and C. M. Hart (2003). Detection of endothelial nitric oxide release with the 2,3-diaminonapthalene assay. Free Radic. Biol. Med. 34, 856–861.CrossRefPubMedGoogle Scholar
  56. 56.
    R. Esquembre, I. Pastor, R. Mallavia, and C. R. Mateo (2005). Fluorometric detection of nitric oxide using 2,3-diaminonaphthalene incorporated in β-cyclodextrin. J. Photochem. Photobiol. A 173, 384–389.CrossRefGoogle Scholar
  57. 57.
    J. K. J. Park and P. Kostka (1997). Fluorometric detection of biological S-nitrosothiols. Anal. Biochem. 249, 61–66.CrossRefPubMedGoogle Scholar
  58. 58.
    M. Kirsch and H. de Groot (2002). Formation of peroxynitrite from reaction of nitroxyl anion with molecular oxygen. J. Biol. Chem. 277, 13379–13388.CrossRefPubMedGoogle Scholar
  59. 59.
    H. Kojima, K. Sakurai, K. Kikuchi, S. Kawahara, Y. Kirino, H. Nagoshi, Y. Hirata, and T. Nagano (1998). Development of a fluorescent indicator for nitric oxide based on the fluorescein chromophore. Chem. Pharm. Bull. 46, 373–375.PubMedGoogle Scholar
  60. 60.
    H. Kojima, N. Kakatsubo, K. Kikuchi, S. Kawahara, Y. Kirino, H. Nagoshi, Y. Hirata, and T. Nagano (1998). Detection and imaging of nitric oxide with novel fluorescent indicators: Diaminofluoresceins. Anal. Chem. 70, 2446–2453.CrossRefPubMedGoogle Scholar
  61. 61.
    N. Nakatsubo, H. Kojima, K. Kikuchi, H. Nagoshi, Y. Hirata, D. Maeda, Y. Imai, T. Irimura, and T. Nagano (1998). Direct evidence of nitric oxide production from bovine aortic endothelial cells using new fluorescence indicators: Diaminofluoresceins. FEBS Lett. 427, 263–266.CrossRefPubMedGoogle Scholar
  62. 62.
    N. Suzuki, H. Kojima, Y. Urano, K. Kikuchi, Y. Hirata, and T. Nagano (2002). Orthogonality of calcium concentration and ability of 4,5-diaminofluorescein to detect NO. J. Biol. Chem. 277, 47–49.CrossRefPubMedGoogle Scholar
  63. 63.
    C. Munkholm, D. R. Parkinson, and D. R. Walt (1990). Intramolecular fluorescence self-quenching of fluoresceinamine. J. Am. Chem. Soc. 112, 2608–2612.CrossRefGoogle Scholar
  64. 64.
    A. R. Kim, Y. Zou, H. S. Kim, J. S. Choi, G. Y. Chang, Y. J. Kim, and H. Y. Chung (2002). Selective peroxynitrite scavenging activity of 3-methyl-1,2-cyclopentanedione from coffee extract. J. Pharm. Pharmacol. 54, 1385–1392.CrossRefPubMedGoogle Scholar
  65. 65.
    E. Fernandes, S. A. Toste, J. L. F. C. Lima, and S. Reis (2003). The metabolism of sulindac enhances its scavenging activity against reactive oxygen and nitrogen species. Free Radic. Biol. Med. 35, 1008–1017.CrossRefPubMedGoogle Scholar
  66. 66.
    E. Fernandes, D. Costa, S. A. Toste, J. L. F. C. Lima, and S. Reis (2004). In vitro scavenging activity for reactive oxygen and nitrogen species by nonsteroidal anti-inflammatory indole, pyrrole, and oxazole derivative drugs. Free Radic. Biol. Med. 37, 1895–1905.CrossRefPubMedGoogle Scholar
  67. 67.
    M. G. Espey, K. M. Miranda, D. D. Thomas, and D. A. Wink (2002). Ingress and reactive chemistry of nitroxyl-derived species within human cells. Free Radic. Biol. Med. 33, 827–834.CrossRefPubMedGoogle Scholar
  68. 68.
    X. Zhang, W. S. Kim, N. Hatcher, K. Potgieter, L. L. Moroz, R. Gillette, and J. V. Sweedler (2002). Interfering with nitric oxide measurements. 4,5-Diaminofluorescein reacts with dehydroascorbic acid and ascorbic acid. J. Biol. Chem. 277, 48472–48478.CrossRefPubMedGoogle Scholar
  69. 69.
    N. Nagata, K. Momose, and Y. Ishida (1999). Inhibitory effects of catecholamines and anti-oxidants on the fluorescence reaction of 4,5-diaminofluorescein, DAF-2, a novel indicator of nitric oxide. J. Biochem. 125, 658–661.PubMedGoogle Scholar
  70. 70.
    J. Rodriguez, V. Specian, R. Maloney, D. Jourd'heuil, and M. Feelisch (2005). Performance of diamino fluorophores for the localization of sources and targets of nitric oxide. Free Radic. Biol. Med. 38, 356–368.CrossRefPubMedGoogle Scholar
  71. 71.
    X. Ye, W. S. Kim, S. S. Rubakhin, and J. V. Sweedler (2004). Measurement of nitric oxide by 4,5-diaminofluorescein without interferences. Analyst 129, 1200–1205.CrossRefPubMedGoogle Scholar
  72. 72.
    D. Jourd'heuil (2002). Increased nitric oxide-dependent nitrosylation of 4,5-diaminofluorescein by oxidants: Implications for the measurement of intracellular nitric oxide. Free Radic. Biol. Med. 33, 676–684.CrossRefPubMedGoogle Scholar
  73. 73.
    H. Kojima, M. Hirotani, N. Kakatsubo, K. Kikuchi, Y. Urano, T. Higuchi, Y. Hirata, and T. Nagano (2001). Bioimaging of nitric oxide with fluorescent indicators based on the rhodamine chromophore. Anal. Chem. 73, 1967–1973.CrossRefPubMedGoogle Scholar
  74. 74.
    T. Imura, S. Kanatani, S. Fukuda, Y. Miyamoto, and T. Hisatsune (2004). Layer-specific production of nitric oxide during cortical circuit formation in postnatal mouse brain. Cereb. Cortex 21, 1–9.Google Scholar
  75. 75.
    P. Heiduschka and S. Thanos (1998). NO production during neuronal cell death can be directly assessed by a chemical reaction in vivo. Neuroreport 9, 4051–4057.PubMedGoogle Scholar
  76. 76.
    O. von Bohlen und Halbach, D. Albrecht, U. Heinemann, and S. Schuchmann (2002). Spatial nitric oxide imaging using 1,2-diaminoanthraquinone to investigate the involvement of nitric oxide in long-term potentiation in rat brain slices. Neuroimage 15, 633–639.CrossRefPubMedGoogle Scholar
  77. 77.
    X. Chen, C. Sheng, and X. Zheng (2001). Direct nitric oxide imaging in cultured hippocampal neurons with diaminoanthraquinone and confocal microscopy. Cell Biol. Int. 25, 593–598.CrossRefPubMedGoogle Scholar
  78. 78.
    S. Schuchmann, D. Albrecht, U. Heinemann, and O. von Bohlen und Halbach (2002). Nitric oxide modulates low-Mg2+-induced epileptiform activity in rat hippocampal–entorhinal cortex slices. Neurobiol. Dis. 11, 96–105.CrossRefPubMedGoogle Scholar
  79. 79.
    P. Meineke, U. Rauen, H. de Groot, and H.-G. Koth (1999). Cheletropic traps for the fluorescence spetroscopic detection of nitric oxide (nitrogen monoxide) in biological systems. Chem. A Eur. J. 5, 1738–1747.CrossRefGoogle Scholar
  80. 80.
    P. Meineke, U. Rauen, H. de Groot, H. G. Korth, and R. Sustmann (2000). Nitric oxide detection and visualization in biological systems. Applications of the FNOCT method. Biol. Chem. 381, 575–582.CrossRefPubMedGoogle Scholar
  81. 81.
    A. Huisman, A. van de Wiel, T. J. Rabelink, and E. E. van Faassen (2004). Wine polyphenols and ethanol do not significantly scavenge superoxide nor affect endothelial nitric oxide production. J. Nutr. Biochem. 15, 426–432.CrossRefPubMedGoogle Scholar
  82. 82.
    A. U. Swintek, S. Christoph, F. Petrat, H. de Groot, and M. Kirsch (2004). Cell type-dependent release of nitric oxide and/or reactive nitrogenoxide species from intracellular SIN-1: Effects on cellular NAD(P)H. Biol. Chem. 385, 639–648.CrossRefPubMedGoogle Scholar
  83. 83.
    K. J. Franz, N. Singh, and S. J. Lippard (2000). Metal-based NO sensing by selective ligand. Angew. Chem. Int. Ed. 39, 2120–2122.CrossRefGoogle Scholar
  84. 84.
    Y. Katayama, N. Soh, and M. Maeda (2001). A new strategy for the design of molecular probes for investigating endogenous nitric oxide using an EPR or fluorescent technique. Chem. Phys. Chem. 2, 655–661.Google Scholar
  85. 85.
    Y. Gabe, Y. Urano, K. Kikuchi, H. Kojima, and T. Nagano (2004). Highly sensitive fluorescence probes for nitric oxide based on boron dipyrromethene chromophore—Rational design of potentially useful bioimaging fluorescence probe. J. Am. Chem. Soc. 126, 3357–3367.CrossRefPubMedGoogle Scholar
  86. 86.
    H. Kojima, K. Sakurai, K. Kikuchi, S. Kawahara, Y. Kirino, H. Nagoshi, Y. Hirata, T. Akaike, H. Maeda, and T. Nagano (1997). Development of a fluorescent indicator for the bioimaging of nitric oxide. Biol. Pharm. Bull. 20, 1229–1232.PubMedGoogle Scholar
  87. 87.
    E. M. Lozinsky, L. V. Martina, A. I. Shames, N. Uzlaner, A. Masarwa, G. I. Likhtenshtein, D. Meyerstein, V. V. Martin, and Z. Priel (2004). Detection of nitric oxide from pig trachea by a fluorescence method. Anal. Biochem. 326, 139–145.CrossRefPubMedGoogle Scholar
  88. 88.
    J. Joseph, B. Kalyanaraman, and J. S. Hyde (1993). Trapping of nitric oxide by nitronyl nitroxides: An electron spin resonance investigation. Biochem. Biophys. Res. Commun. 192, 926–934.CrossRefPubMedGoogle Scholar
  89. 89.
    Y. Y. Woldman, V. V. Khramtsov, I. A. Grigor'ev, I. A. Kiriljuk, and D. I. Utepbergenov (1994). Spin trapping of nitric oxide by nitronylnitroxides: Measurement of the activity of NO synthase from rat cerebellum. Biochem. Biophys. Res. Commun. 202, 195–203.CrossRefPubMedGoogle Scholar
  90. 90.
    E. Lozinsky, V. V. Martin, T. A. Berezina, A. I. Shames, A. L. Weis, and G. I. Likhtenshtein (1999). Dual fluorophore-nitroxide probes for analysis of vitamin C in biological liquids. J. Biochem. Biophys. Methods 38, 29–42.CrossRefPubMedGoogle Scholar
  91. 91.
    N. W. Kooy, J. A. Royall, H. Ischiropoulos, and J. S. Beckman (1994). Peroxynitrite-mediated oxidation of dihydrorhodamine 123. Free Radic. Biol. Med. 16, 149–156.CrossRefPubMedGoogle Scholar
  92. 92.
    J. P. Crow (1997). Dichlorodihydrofluorescein and dihydrorhodamine 123 are sensitive indicators of peroxynitrite in vitro: Implications for intracellular measurement of reactive nitrogen and oxygen species. Nitric Oxide 1, 145–157.CrossRefPubMedGoogle Scholar
  93. 93.
    D. Jourd'heuil, F. L. Jourd'heuil, P. S. Kutchukian, R. A. Musah, D. A. Wink, and M. B. Grisham (2001). Reaction of superoxide and nitric oxide with peroxynitrite. Implications for peroxynitrite-mediated oxidation reactions in vivo. J. Biol. Chem. 276, 28799–28805.CrossRefPubMedGoogle Scholar
  94. 94.
    J. Glebska and W. H. Koppenol (2003). Peroxynitrite-mediated oxidation of dichlorodihydrofluorescein and dihydrorhodamine. Free Radic. Biol. Med. 35, 676–682.CrossRefPubMedGoogle Scholar
  95. 95.
    Y. Zou, A. R. Kim, J. E. Kim, J. S. Choi, and H. Y. Chung (2002). Peroxynitrite scavenging activity of synaptic acid (3,5-dimethoxy-4-hydroxycinnamic acid) isolated from Brassica juncea. J. Agric. Food Chem. 50, 5884–5890.CrossRefPubMedGoogle Scholar
  96. 96.
    F. Bailly, V. Zoete, J. Vamecq, J. P. Catteau, and J. L. Bernier (2000). Antioxidant actions of ovothiol-derived 4-mercaptoimidazoles: Glutathione peroxidase activity and protection against peroxynitrite-induced damage. FEBS Lett. 486, 19–22.CrossRefPubMedGoogle Scholar
  97. 97.
    J. S. Choi, H. Y. Chung, S. S. Kang, M. J. Jung, J. W. Kim, J. K. No, and H. A. Jung (2002). The structure–activity relationship of flavonoids as scavengers of peroxynitrite. Phytother. Res. 16, 232–235.CrossRefPubMedGoogle Scholar
  98. 98.
    M. Wrona, K. Patel, and P. Wardman (2005). Reactivity of 2′,7′-dichloro-dihydrofluorescein and dihydrorhodamine 123 and their oxidized forms toward carbonate, nitrogen dioxide, and hydroxyl radicals. Free Radic. Biol. Med. 38, 262–270.CrossRefPubMedGoogle Scholar
  99. 99.
    J. A. Royall and H. Ischiropoulos (1993). Evaluation of 2′,7′-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. Arch. Biochem. Biophys. 302, 348–355.CrossRefPubMedGoogle Scholar
  100. 100.
    L. M. Henderson and J. B. Chappell (1993). Dihydrorhodamine 123: A fluorescent probe for superoxide generation? Eur. J. Biochem. 217, 973–980.CrossRefPubMedGoogle Scholar
  101. 101.
    S. L. Hempel, G. R. Buettner, Y. Q. O'Malley, D. A. Wessels, and D. M. Flaherty (1999). Dihydrofluorescein diacetate is superior for detecting intracellular oxidants: Comparison with 2′,7′-dichlorodihydrofluorescein diacetate, 5(and 6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate, and dihydrorhodamine 123. Free Radic. Biol. Med. 27, 146–159.CrossRefPubMedGoogle Scholar
  102. 102.
    A. S. Keston and R. Brandt (1965). The fluorometric analysis of ultramicro quantities of hydrogen peroxide. Anal. Biochem. 11, 1–5.CrossRefPubMedGoogle Scholar
  103. 103.
    N. W. Kooy, J. A. Royall, and H. Ischiropoulos (1997). Oxidation of 2′,7′-dichlorofluorescin by peroxynitrite. Free Radic. Res. 27, 245–254.PubMedGoogle Scholar
  104. 104.
    H. Wang and J. A. Joseph (1999). Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic. Biol. Med. 27, 612–616.CrossRefPubMedGoogle Scholar
  105. 105.
    K. M. Rao, J. Padmanabhan, D. L. Kilby, H. J. Cohen, M. S. Currie, and J. B. Weinberg (1992). Flow cytometric analysis of nitric oxide production in human neutrophils using dichlorofluorescein diacetate in the presence of a calmodulin inhibitor. J. Leukoc. Biol. 51, 496–500.PubMedGoogle Scholar
  106. 106.
    P. G. Gunasekar, A. G. Kanthasamy, J. L. Borowitz, and G. E. Isom (1995). Monitoring intracellular nitric oxide formation by dichlorofluorescin in neuronal cells. J. Neurosci. Methods 61, 15–21.CrossRefPubMedGoogle Scholar
  107. 107.
    H. Possel, H. Noack, W. Augustin, G. Keilhoff, and G. Wolf (1997). 2,7-Dihydrodichlorofluorescein diacetate as a fluorescent marker for peroxynitrite formation. FEBS Lett. 416, 175–178.CrossRefPubMedGoogle Scholar
  108. 108.
    O. Myhre, J. M. Andersen, H. Aarnes, and F. Fonnum (2003). Evaluation of the probes 2′,7′-dichlorofluorescin diacetate, luminol, and lucigenin as indicators of reactive species formation. Biochem. Pharmacol. 65, 1575–1582.CrossRefPubMedGoogle Scholar
  109. 109.
    D. A. Bass, J. W. Parce, L. R. Dechatelet, P. Szejda, M. C. Seeds, and M. Thomas (1983). Flow cytometric studies of oxidative product formation by neutrophils: A graded response to membrane stimulation. J. Immunol. 130, 1910–1917.PubMedGoogle Scholar
  110. 110.
    X.-F. Yang, X.-Q. Guo, and Y.-B. Zhao (2002). Development of a novel rhodamine-type fluorescent probe to determine peroxynitrite. Talanta 57, 883–890.PubMedGoogle Scholar
  111. 111.
    R. Radi, G. Peluffo, M. N. Alvarez, M. Naviliat, and A. Cayota (2001). Unraveling peroxynitrite formation in biological systems. Free Radic. Biol. Med. 30, 463–488.CrossRefPubMedGoogle Scholar
  112. 112.
    K. Setsukinai, Y. Urano, K. Kakinuma, H. J. Majima, and T. Nagano (2003). Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J. Biol. Chem. 278, 3170–3175.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Ana Gomes
    • 1
  • Eduarda Fernandes
    • 1
  • José L. F. C. Lima
    • 1
  1. 1.REQUIMTE, Departamento de Química-Fisica, Faculdade de FarmáciaUniversidade do PortoPortoPortugal

Personalised recommendations