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Biological Relevance of Free Radicals and Nitroxides

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Abstract

Nitroxides are stable, kinetically-persistent free radicals which have been successfully used in the study and intervention of oxidative stress, a critical issue pertaining to cellular health which results from an imbalance in the levels of damaging free radicals and redox-active species in the cellular environment. This review gives an overview of some of the biological processes that produce radicals and other reactive oxygen species with relevance to oxidative stress, and then discusses interactions of nitroxides with these species in terms of the use of nitroxides as redox-sensitive probes and redox-active therapeutic agents

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References

  1. Neta, P., Grodkowski, J., & Ross, A. (1996). Rate constants for reactions of aliphatic carbon‐centered radicals in aqueous solution. Journal of Physical and Chemical Reference Data, 25, 709–1050.

    Article  CAS  Google Scholar 

  2. Bakač, A. (1994). Radical kinetics as a mechanistic and analytical tool. Croatica Chemica Acta., 66, 435–445.

    Google Scholar 

  3. Minakata, D., & Crittenden, J. (2011). Linear free energy relationships between aqueous phase hydroxyl radical reaction rate constants and free energy of activation. Environmental Science & Technology, 45, 3479–3486.

    Article  CAS  Google Scholar 

  4. Reiter, R., Tan, D., & Burkhardt, S. (2002). Reactive oxygen and nitrogen species and cellular and organismal decline: amelioration with melatonin. Mechanisms of Ageing and Development, 123, 1007–1019.

    Article  CAS  PubMed  Google Scholar 

  5. Lam, M., Pattison, D., Bottle, S., Keddie, D., & Davies, M. (2008). Nitric oxide and nitroxides can act as efficient scavengers of protein-derived free radicals. Chemical Research in Toxicology, 21, 2111–2119.

    Article  CAS  PubMed  Google Scholar 

  6. Wiseman, H., & Halliwell, B. (1996). Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochemical Journal, 313, 17–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Babcock, G. (1999). How oxygen is activated and reduced in respiration. Proceedings of the National Academy of Sciences of the United States of America, 96, 12971–12973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Schieber, M., & Chandel, N. (2014). ROS function in redox signaling and oxidative stress. Current Biology, 24, R453–R462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Storz, P. (2005). Reactive oxygen species in tumour progression. Frontiers in Bioscience, 10, 1881–1896.

    Article  CAS  PubMed  Google Scholar 

  10. Ji, J., et al. (2012). Lipidomics identifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury. Nature Neuroscience, 15, 1407–1413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Varadarajan, S., Yatin, S., Aksenova, M., & Butterfield, D. (2000). Review: alzheimer’s amyloid β-peptide-associated free radical oxidative stress and neurotoxicity. Journal of Structural Biology, 130, 184–208.

    Article  CAS  PubMed  Google Scholar 

  12. Krishna, M., Halevy, R., Zhang, R., Gutierrez, P., & Samuni, A. (1994). Modulation of streptonigrin cytotoxicity by nitroxide SOD mimics. Free Radical Biology and Medicine, 17, 379–388.

    Article  CAS  PubMed  Google Scholar 

  13. Catterall, H., Davies, M., Gilbert, B., & Polack, N. (1993). EPR spin-trapping studies of the reaction of the hydroxyl radical with pyrimidine nucleobases, nucleosides and nucleotides, polynucleotides, and RNA. Direct evidence for sites of initial attack and for strand breakage. Journal of the Chemical Society, Perkin Transactions, 2, 2039–2047.

    Article  Google Scholar 

  14. Aronovitch, Y., Godinger, D., Israeli, A., Krishna, M., Samuni, A., & Goldstein, S. (2007). Dual activity of nitroxides as pro- and antioxidants: Catalysis of copper-mediated DNA breakage and H2O2 dismutation. Free Radical Biology and Medicine, 42, 1317–1325.

    Article  CAS  PubMed  Google Scholar 

  15. Saeed, S., et al. (2010). Interactions of cyclooxygenase inhibitors with reactive oxygen species. Journal of Pharmacology and Toxicology, 5, 487–497.

    CAS  Google Scholar 

  16. Hoffman, A., Goldstein, S., Samuni, S., Borman, J., & Schwalb, H. (2003). Effect of nitric oxide and nitroxide SOD-mimic on the recovery of isolated rat heart following ischemia and reperfusion. Biochemical Pharmacology, 66, 1279–1286.

    Article  CAS  PubMed  Google Scholar 

  17. Macias, C., et al. (2007). Treatment with a novel hemigramicidin-TEMPO conjugate prolongs survival in a rat model of lethal hemorrhagic shock. Annals of Surgery, 245, 305–314.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fu, S., Davies, M., Stocker, R., & Dean, R. (1998). Evidence for roles of radicals in protein oxidation in advanced human atherosclerotic plaque. Biochemical Journal, 333, 519–525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Davies, M., Hawkins, C., Pattison, D., & Rees, M. (2008). Mammalian heme peroxidases: From molecular mechanisms to health implications. Antioxidants & Redox Signaling, 10, 1199–1234.

    Article  CAS  Google Scholar 

  20. Hosokawa, K., Chen, P., Lavin, M., & Bottle, S. (2004). The impact of carboxy nitroxide antioxidants on irradiated ataxia telangiectasia cells. Free Radical Biology and Medicine, 37, 946–952.

    Article  CAS  PubMed  Google Scholar 

  21. Xun, Z., et al. (2012). Targeting of XJB-5-131 to Mitochondria suppresses oxidative DNA damage and motor decline in a mouse model of Huntington’s disease. Cell Reports, 2, 1137–1142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lipman, T., Tabakman, R., & Lazarovici, P. (2006). Neuroprotective effects of the stable nitroxide compound Tempol on 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in the Nerve Growth Factor-differentiated model of pheochromocytoma PC12 cells. European Journal of Pharmacology, 549, 50–57.

    Article  CAS  PubMed  Google Scholar 

  23. Silva, D., Belini, E., de Almeida, E., & Bonini-Domingos, C. (2013). Oxidative stress in sickle cell disease: An overview of erythrocyte redox metabolism and current antioxidant therapeutic strategies. Free Radical Biology and Medicine, 65, 1101–1109.

    Article  CAS  PubMed  Google Scholar 

  24. Jiang, J., et al. (2008). A mitochondria-targeted nitroxide/hemigramicidin S conjugate protects mouse embryonic cells against gamma irradiation. International Journal of Radiation Oncology Biology Physics, 70, 816–825.

    Article  CAS  Google Scholar 

  25. Zhou, B., et al. (2012). Baicalin protects human skin fibroblasts from ultraviolet A radiation-induced oxidative damage and apoptosis. Free Radical Research, 46, 1458–1471.

    Article  CAS  PubMed  Google Scholar 

  26. Jiang, J., et al. (2007). Structural requirements for optimized delivery, inhibition of oxidative stress, and antiapoptotic activity of targeted nitroxides. Journal of Pharmacology and Experimental Therapeutics, 320, 1050–1060.

    Article  CAS  PubMed  Google Scholar 

  27. Fu, S., Dean, R., Southan, M., & Truscott, R. (1998). The hydroxyl radical in lens nuclear cataractogenesis. Journal of Biological Chemistry, 273, 28603–28609.

    Article  CAS  PubMed  Google Scholar 

  28. Tyurina, Y., et al. (2010). Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation. American Journal of Physiology-Lung Cellular and Molecular Physiology, 299, L73–L85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Long, H., et al. (2004). ROS-mediated TNF-α and MIP-2 gene expression in alveolar macrophages exposed to pine dust. Particle and Fibre Toxicology, 1, 1–8.

    Article  CAS  Google Scholar 

  30. Samuni, A., Karmeli, F., Moshen, M., & Rachmilewitz, D. (1999). Mechanisms underlying gastric antiulcerative activity of nitroxides in rats. Free Radical Research, 30, 133–140.

    Article  CAS  PubMed  Google Scholar 

  31. Ryu, S., Kohen, R., Samuni, A., & Ornoy, A. (2007). Nitroxide radicals protect cultured rat embryos and yolk sacs from diabetic-induced damage. Birth Defects Research Part A-Clinical and Molecular Teratology, 79, 604–611.

    Article  CAS  Google Scholar 

  32. Rahimi, R., Nikfar, S., Larijani, B., & Abdollahi, M. (2005). A review on the role of antioxidants in the management of diabetes and its complications. Biomedicine & Pharmacotherapy, 59, 365–373.

    Article  CAS  Google Scholar 

  33. Gutteridge, J. (1993). Free radicals in disease processes: A compilation of cause and consequence. Free Radical Research Communications, 19, 141–158.

    Article  CAS  PubMed  Google Scholar 

  34. Ernster, L., & Schatz, G. (1981). Mitochondria: A historical review. The Journal of Cell Biology, 91, 227s–255s.

    Article  CAS  PubMed  Google Scholar 

  35. Prousek, J. (2007). Fenton chemistry in biology and medicine. Pure and Applied Chemistry, 79, 2325–2338.

    Article  CAS  Google Scholar 

  36. Kehrer, J. (2000). The Haber–Weiss reaction and mechanisms of toxicity. Toxicology, 149, 43–50.

    Article  CAS  PubMed  Google Scholar 

  37. Rittle, J., & Green, M. (2010). Cytochrome P450 compound I: Capture, characterization, and C–H bond activation kinetics. Science, 330, 933–937.

    Article  CAS  PubMed  Google Scholar 

  38. Rees, M., Bottle, S., Fairfull‑Smith, K., Malle, E., Whitelock, J., & Davies, M. (2009). Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides. Biochemical Journal, 421, 79–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Klebanoff, S. (2005). Myeloperoxidase: Friend and foe. Journal of Leukocyte Biology, 77, 598–625.

    Article  CAS  PubMed  Google Scholar 

  40. Zhelev, Z., Aoki, I., Gadjeva, V., Nikolova, B., Bakalova, R., & Saga, T. (2013). Tissue redox activity as a sensing platform for imaging of cancer based on nitroxide redox cycle. European Journal of Cancer, 49, 1467–1478.

    Article  CAS  PubMed  Google Scholar 

  41. Koekkoek, W., van Zanten, A. (2016). Antioxidant vitamins and trace elements in critical illness. Nutrition in Clinical Practice. first published on June 16, 2016.

  42. Matés, J., & Sánchez-Jiménez, F. (2000). Role of reactive oxygen species in apoptosis: implications for cancer therapy. The International Journal of Biochemistry & Cell Biology, 32, 157–170.

    Article  Google Scholar 

  43. Kawamukai, M. (2016). Biosynthesis of coenzyme Q in eukaryotes. Bioscience, Biotechnology, and Biochemistry, 80, 23–33.

    CAS  Google Scholar 

  44. Wang, Y., & Hekimi, S. (2016). Understanding ubiquinone. Trends in cell biology, 26, 367–378.

    Article  CAS  PubMed  Google Scholar 

  45. Niki, E. (1987). Interaction of ascorbate and α-tocopherol. Annals of the New York Academy of Sciences, 498, 186–199.

    Article  CAS  PubMed  Google Scholar 

  46. Doonan, S., Bara, D., & Bossa, F. (1984). Structural and genetic relationships between cytosolic and mitochondrial isoenzymes. International Journal of Biochemistry, 16, 1193–1199.

    Article  CAS  PubMed  Google Scholar 

  47. Dringen, R., Pawlowski, P., & Hirrlinger, J. (2004). Peroxide detoxification by brain cells. Journal of Neuroscience Research, 79, 157–165.

    Article  CAS  Google Scholar 

  48. Amar, M., et al. (2015). Design concept for α-hydrogen-substituted nitroxides. Nature Communications, 6, 6070.

    Article  CAS  PubMed  Google Scholar 

  49. Bagryanskaya, E., & Marque, S. (2014). Scavenging of organic C-centered radicals by nitroxides. Chemical Reviews, 114, 5011–5056.

    Article  CAS  PubMed  Google Scholar 

  50. Becker, M., De Cola, L., & Studer, A. (2011). Site-specific immobilization of proteins at zeolite L crystals by nitroxide exchange reactions. Chemical Communucations, 47, 3392–3394.

    Article  CAS  Google Scholar 

  51. Schulte, B., Tsotsalas, M., Becker, M., Studer, A., & De Cola, L. (2010). Dynamic microcrystal assembly by nitroxide exchange reactions. Angewandte Chemie, International Edition, 49, 6881–6884.

    Article  CAS  Google Scholar 

  52. Lowe, A., & McCormick, C. (2002). Homogeneous controlled free radical polymerization in aqueous media. Australian Journal of Chemistry, 55, 367–379.

    Article  CAS  Google Scholar 

  53. Lalevée, J., Gigmes, D., Bertin, D., Allonas, X., & Fouassier, J. (2007). Interaction of monomer radicals with nitroxides: A new access to the radical–radical combination rate constants. Chemical Physics Letters, 449, 231–235.

    Article  CAS  Google Scholar 

  54. Moncelet, D., et al. (2014). Alkoxyamines: Toward a new family of theranostic agents against cancer. Molecular Pharmaceutics, 11, 2412–2419.

    Article  CAS  PubMed  Google Scholar 

  55. Sahu, I., McCarrick, R., & Lorigan, G. (2013). Use of electron paramagnetic resonance to solve biochemical problems. Biochemistry, 52, 5967–5984.

    Article  CAS  PubMed  Google Scholar 

  56. Swartz, H., et al. (2014). Clinical EPR: Unique opportunities and some challenges. Academic Radiology, 21, 197–206.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Berliner, L., & Fujii, H. (1985). Magnetic resonance imaging of biological specimens by electron paramagnetic resonance of nitroxide spin labels. Science, 227, 517–519.

    Article  CAS  PubMed  Google Scholar 

  58. Matsumoto, K., et al. (2006). High-resolution mapping of tumor redox status by magnetic resonance imaging using nitroxides as redox-sensitive contrast agents. Clinical Cancer Research, 12, 2455–2462.

    Article  CAS  PubMed  Google Scholar 

  59. Hyodo, F., et al. (2008). Assessment of tissue redox status using metabolic responsive contrast agents and magnetic resonance imaging. Journal of Pharmacy and Pharmacology, 60, 1049–1060.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sowers, M., et al. (2014). Redox-responsive branched-bottlebrush polymers for in vivo MRI and fluorescence imaging. Nature Communications, 5, 5460.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Matko, J., Ohki, K., & Edidin, M. (1992). Luminescence quenching by nitroxide spin labels in aqueous solution: Studies on the mechanism of quenching. Biochemistry, 31, 703–711.

    Article  CAS  PubMed  Google Scholar 

  62. Aliaga, C., Fuentealba, P., Rezende, M., & Cárdenas, C. (2014). Mechanism of fluorophore quenching in a pre-fluorescent nitroxide probe: A theoretical illustration. Chemical Physics Letters, 593, 89–92.

    Article  CAS  Google Scholar 

  63. Sylvester, P., Ryan, H., Smith, C., Micallef, A., Schiesser, C., & Wille, U. (2013). Perylene-based profluorescent nitroxides for the rapid monitoring of polyester degradation upon weathering: An assessment. Polymer Degradation and Stability, 98, 2054–2062.

    Article  CAS  Google Scholar 

  64. Blinco, J., Fairfull-Smith, K., Morrow, B., & Bottle, S. (2011). Profluorescent nitroxides as sensitive probes of oxidative change and free radical reactions. Australian Journal of Chemistry, 64, 373–389.

    Article  CAS  Google Scholar 

  65. Blinco, J., Keddie, D., Wade, T., Barker, P., George, G., & Bottle, S. (2008). Profluorescent nitroxides: Sensors and stabilizers of radical-mediated oxidative damage. Polymer Degradation and Stability, 93, 1613–1618.

    Article  CAS  Google Scholar 

  66. Morrow, B., Keddie, D., Gueven, N., Lavin, M., & Bottle, S. (2010). A novel profluorescent nitroxide as a sensitive probe for the cellular redox environment. Free Radical Biology and Medicine, 49, 67–76.

    Article  CAS  PubMed  Google Scholar 

  67. Lozinsky, E., Martin, V., Berezina, T., Shames, A., Weis, A., & Likhtenshtein, G. (1999). Dual fluorophore-nitroxide probes for analysis of vitamin C in biological liquids. Journal of Biochemical and Biophysical Methods, 38, 29–42.

    Article  CAS  PubMed  Google Scholar 

  68. Maki, T., Soh, N., Nakano, K., & Imato, T. (2011). Flow injection fluorometric determination of ascorbic acid using perylenebisimide-linked nitroxide. Talanta, 85, 1730–1733.

    Article  CAS  PubMed  Google Scholar 

  69. Belikova, N., et al. (2011). A high-throughput screening assay of ascorbate in brain samples. Journal of Neuroscience Methods, 201, 185–190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Matsuoka, Y., Yamato, M., Yamasaki, T., Mito, F., & Yamada, K. (2012). Rapid and convenient detection of ascorbic acid using a fluorescent nitroxide switch. Free Radical Biology and Medicine, 53, 2112–2118.

    Article  CAS  PubMed  Google Scholar 

  71. Nam, H., et al. (2016). Highly sensitive and selective fluorescent probe for ascorbic acid with a broad detection range through dual quenching and bimodal action of nitronyl-nitroxide. ACS Sensors, 1, 392–398.

    Article  CAS  Google Scholar 

  72. Frantz, M., et al. (2013). Synthesis of analogs of the radiation mitigator JP4-039 and visualization of BODIPY derivatives in mitochondria. Organic & Biomolecular Chemistry, 11, 4147–4153.

    Article  CAS  Google Scholar 

  73. Ahn, H., et al. (2012). Two-photon fluorescence microscopy imaging of cellular oxidative stress using profluorescent nitroxides. Journal of the American Chemical Society, 134, 4721–4730.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Cao, L., Wu, Q., Li, Q., Shao, S., & Guo, Y. (2013). Visualizing the changes in the cellular redox environment using a novel profluorescent rhodamine nitroxide probe. New Journal of Chemistry, 37, 2991–2994.

    Article  CAS  Google Scholar 

  75. Hirosawa, S., Arai, S., & Takeoka, S. (2012). A TEMPO-conjugated fluorescent probe for monitoring mitochondrial redox reactions. Chemical Communications, 40, 4845–4847.

    Article  CAS  Google Scholar 

  76. Blinco, J., McMurtrie, J., & Bottle, S. (2007). The first example of an azaphenalene profluorescent nitroxide. European Journal of Organic Chemistry, 2007, 4638–4641.

    Article  CAS  Google Scholar 

  77. Wilcox, C. (2010). Effects of tempol and redox-cycling nitroxides in models of oxidative stress. Pharmacology & Therapeutics, 126, 119–145.

    Article  CAS  Google Scholar 

  78. Yoshitomi, T., & Nagasaki, Y. (2011). Nitroxyl radical-containing nanoparticles for novel nanomedicine against oxidative stress injury. Nanomedicine, 6, 509–518.

    Article  CAS  PubMed  Google Scholar 

  79. Rayner, C., Bottle, S., Gole, G., Ward, M., & Barnett, N. (2016). Real-time quantification of oxidative stress and the protective effect of nitroxide antioxidants. Neurochemistry International, 92, 1–12.

    Article  CAS  PubMed  Google Scholar 

  80. Hardeland, R. (2005). Antioxidative protection by melatonin: Multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine, 27, 119–130.

    Article  CAS  PubMed  Google Scholar 

  81. Shen, J., et al. (2002). Development of isoindoline nitroxides for EPR oximetry in viable systems. Applied Magnetic Resonance, 22, 357–368.

    Article  CAS  Google Scholar 

  82. Offer, T., Mohsen, M., & Samuni, A. (1998). An SOD-mimicry mechanism underlies the role of nitroxides in protecting papain from oxidative inactivation. Free Radical Biology and Medicine, 25, 832–838.

    Article  CAS  PubMed  Google Scholar 

  83. Batinić-Haberle, I., Rebouças, J., & Spasojević, I. (2010). Superoxide dismutase mimics: Chemistry, pharmacology, and therapeutic potential. Antioxidants & Redox Signaling, 13, 877–918.

    Article  CAS  Google Scholar 

  84. Zhang, R., Goldstein, S., & Samuni, A. (1999). Kinetics of superoxide-induced exchange among nitroxide antioxidants and their oxidized and reduced forms. Free Radical Biology and Medicine, 26, 1245–1252.

    Article  CAS  PubMed  Google Scholar 

  85. Zeltcer, G., Berensritin, E., Samuni, A., & Chevion, M. (1997). Nitroxide radicals prevent metal-aggravated reperfusion injury in isolated rat heart. Free Radical Research, 27, 627–635.

    Article  CAS  PubMed  Google Scholar 

  86. Samuni, A., Winkelsberg, D., Pinson, A., Hahn, S., Mitchell, J., & Russo, A. (1991). Nitroxide stable radicals protect beating cardiomyocytes against oxidative damage. Journal of Clinical Investigation, 87, 1526–1530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhang, R., Pinson, A., & Samuni, A. (1997). Both hydroxylamine and nitroxide protect cardiomyocytes from oxidative stress. Free Radical Biology and Medicine, 24, 66–75.

    Article  CAS  Google Scholar 

  88. Soule, B., et al. (2007). The chemistry and biology of nitroxide compounds. Free Radical Biology and Medicine, 42, 1632–1650.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Kajer, T., et al. (2014). Inhibition of myeloperoxidase- and neutrophil-mediated oxidant production by tetraethyl and tetramethyl nitroxides. Free Radical Biology and Medicine, 70, 96–105.

    Article  CAS  PubMed  Google Scholar 

  90. Krishna, M., Samuni, A., Taira, J., Goldstein, S., Mitchell, J., & Russo, A. (1996). Stimulation by nitroxides of catalase-like activity of hemeproteins kinetics and mechansim. The Journal of Biological Chemistry, 271, 26018–26025.

    Article  CAS  PubMed  Google Scholar 

  91. Samuni, A., Goldstein, S., Russo, A., Mitchell, J., Krishna, M., & Neta, P. (2002). Kinetics and mechanism of hydroxyl radical and OH-adduct radical reactions with nitroxides and with their hydroxylamines. Journal of the American Chemical Society, 124, 8719–8724.

    Article  CAS  PubMed  Google Scholar 

  92. Goldstein, S., & Samuni, A. (2007). Kinetics and mechanism of peroxyl radical reactions with nitroxides. Journal of Physical Chemistry A, A 111, 1066–1072.

    Article  CAS  Google Scholar 

  93. Goldstein, S., & Samuni, A. (2010). Biologically relevant chemistry of nitroxides. Stable Radicals, 2010, 567–578.

    Article  Google Scholar 

  94. Goldstein, S., Samuni, A., & Merenyi, G. (2008). Kinetics of the reaction between nitroxide and thiyl radicals: Nitroxides as antioxidants in the presence of thiols. Journal of Physical Chemistry A, 112, 8600–8605.

    Article  CAS  Google Scholar 

  95. Augusto, O., Trindade, D., Linares, E., & Vaz, S. (2008). Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants:Mechanisms and implications. Anais da Academia Brasileira de Ciencias, 80, 179–189.

    Article  CAS  PubMed  Google Scholar 

  96. Goldstein, S., Samuni, A., & Merenyi, G. (2004). Reactions of nitric oxide, peroxynitrite, and carbonate radicals with nitroxides and their corresponding oxoammonium cations. Chemical Research in Toxicology, 17, 250–257.

    Article  CAS  PubMed  Google Scholar 

  97. Sadowska-Bartosz, I., Gajewska, A., Skolimowski, J., Szewczyk, R., & Bartosz, G. (2015). Nitroxides protect against peroxynitrite-induced nitration and oxidation. Free Radical Biology and Medicine, 89, 1165–1175.

    Article  CAS  PubMed  Google Scholar 

  98. Głębska, J., Skolimowski, J., Kudzin, Z., Gwoździński, K., Grzelak, A., & Bartosz, G. (2003). Pro-oxidative activity of nitroxides in their reactions with glutathione. Free Radical Biology and Medicine, 35, 310–316.

    Article  PubMed  CAS  Google Scholar 

  99. Merbouh, N., Bobbitt, J., & Brückner, C. (2004). Preparation of tetramethylpiperidine-1-oxoammonium salts and their use as oxidants in organic chemistry. A review. Organic Preparations and Procedures International, 36, 3–31.

    Article  CAS  Google Scholar 

  100. Offer, T., Russo, A., & Samuni, A. (2000). The pro-oxidative activity of SOD and nitroxide SOD mimics. FASEB Journal, 14, 1215–1223.

    CAS  PubMed  Google Scholar 

  101. Damiana, E., et al. (2000). The effects of nitroxide radicals on oxidative DNA damage. Free Radical Biology and Medicine, 28, 1257–1265.

    Article  Google Scholar 

  102. Sigma-Aldrich. June 2016. TEMPO. Product Number: 214000.

  103. Frantz, M., et al. (2011). Large-scale asymmetric synthesis of the bioprotective agent JP4-039 and analogs. Organic Letters, 13, 2318–2321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Smith, R., et al. (2008). Mitochondria-targeted antioxidants in the treatment of disease. Annals of the New York Academy of Sciences, 1147, 105–111.

    Article  CAS  PubMed  Google Scholar 

  105. Hoye, A., Davoren, J., Wipf, P., Fink, M., & Kagan, V. (2008). Targeting mitochondria. Accounts of Chemical Research, 41, 87–97.

    Article  CAS  PubMed  Google Scholar 

  106. Lavin, M., Gueven, N., Bottle, S., & Gatti, R. (2007). Current and potential therapeutic strategies for the treatment of ataxia-telangiectasia. British Medical Bulletin, 81-82, 129–147.

    Article  PubMed  CAS  Google Scholar 

  107. Pacher, P., Beckman, J., & Liaudet, L. (2007). Nitric oxide and peroxynitrite in health and disease. Physiological Reviews, 87, 315–424.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Davis, R., et al. (2011). A novel nitroxide is an effective brain redox imaging contrast agent and in vivo radioprotector. Free Radical Biology and Medicine, 51, 780–790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Prescott, C., Bottle, S.E. Biological Relevance of Free Radicals and Nitroxides. Cell Biochem Biophys 75, 227–240 (2017). https://doi.org/10.1007/s12013-016-0759-0

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