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Sagai M, Bocci V. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?. Med Gas Res. 2011;1:29doi: 10.1186/2045-9912-1-29.
Sagai, M., & Bocci, V. (2011). Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?. Medical gas research, 129. https://doi.org/10.1186/2045-9912-1-29
Sagai, Masaru, and Bocci, Velio. "Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?." Medical gas research vol. 1 (2011): 29. doi: https://doi.org/10.1186/2045-9912-1-29
Sagai M, Bocci V. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?. Med Gas Res. 2011 Dec 20;1:29. doi: 10.1186/2045-9912-1-29. PMID: 22185664; PMCID: PMC3298518.
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Med Gas Res. 2011 Dec 20;1:29. doi: 10.1186/2045-9912-1-29.

Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?.

Medical gas research

Masaru Sagai, Velio Bocci

Affiliations

  1. Department of Physiology, Viale A, Moro 2, 53100, University of Siena, Italy. [email protected].

PMID: 22185664 PMCID: PMC3298518 DOI: 10.1186/2045-9912-1-29

Abstract

The potential mechanisms of action of ozone therapy are reviewed in this paper. The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not.Severe oxidative stress activates nuclear transcriptional factor kappa B (NFκB), resulting in an inflammatory response and tissue injury via the production of COX2, PGE2, and cytokines. However, moderate oxidative stress activates another nuclear transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 then induces the transcription of antioxidant response elements (ARE). Transcription of ARE results in the production of numerous antioxidant enzymes, such as SOD, GPx, glutathione-s-transferase(GSTr), catalase (CAT), heme-oxygenase-1 (HO-1), NADPH-quinone-oxidoreductase (NQO-1), phase II enzymes of drug metabolism and heat shock proteins (HSP). Both free antioxidants and anti-oxidative enzymes not only protect cells from oxidation and inflammation but they may be able to reverse the chronic oxidative stress. Based on these observations, ozone therapy may also activate Nrf2 via moderate oxidative stress, and suppress NFκB and inflammatory responses. Furthermore, activation of Nrf2 results in protection against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Mild immune responses are induced via other nuclear transcriptional factors, such as nuclear factor of activated T-cells (NFAT) and activated protein-1 (AP-1).Additionally, the effectiveness of ozone therapy in vascular diseases may also be explained by the activation of another nuclear transcriptional factor, hypoxia inducible factor-1α (HIF-1a), which is also induced via moderate oxidative stress. Recently these concepts have become widely accepted. The versatility of ozone in treating vascular and degenerative diseases as well as skin lesions, hernial disc and primary root carious lesions in children is emphasized. Further researches able to elucidate whether the mechanisms of action of ozone therapy involve nuclear transcription factors, such as Nrf2, NFAT, AP-1, and HIF-1α are warranted.

References

  1. Free Radic Biol Med. 2011 Jul 1;51(1):88-96 - PubMed
  2. Am J Respir Cell Mol Biol. 2006 Feb;34(2):174-81 - PubMed
  3. Science. 1980 Aug 22;209(4459):931-3 - PubMed
  4. Wound Repair Regen. 2011 Jan-Feb;19(1):107-15 - PubMed
  5. Cardiovasc Hematol Disord Drug Targets. 2009 Jun;9(2):78-85 - PubMed
  6. Int J Artif Organs. 2005 Oct;28(10):1039-50 - PubMed
  7. Science. 2009 Jul 10;325(5937):201-4 - PubMed
  8. J Altern Complement Med. 2005 Apr;11(2):257-65 - PubMed
  9. Int J Cancer. 2008 Sep 1;123(5):1222; author reply 1223 - PubMed
  10. AJNR Am J Neuroradiol. 2003 May;24(5):996-1000 - PubMed
  11. Free Radic Biol Med. 2008 Jan 15;44(2):126-31 - PubMed
  12. Br J Biomed Sci. 2007;64(1):44-9 - PubMed
  13. Acta Biochim Pol. 2000;47(4):889-99 - PubMed
  14. Biochem Pharmacol. 1997 Apr 4;53(7):1061-4 - PubMed
  15. Arch Toxicol. 2011 Apr;85(4):273-84 - PubMed
  16. Cell Cycle. 2009 Oct 15;8(20):3255-6 - PubMed
  17. Antioxid Redox Signal. 2010 Mar 1;12(5):641-55 - PubMed
  18. Free Radic Biol Med. 2004 Sep 1;37(5):597-606 - PubMed
  19. J Biol Regul Homeost Agents. 1998 Jul-Sep;12(3):67-75 - PubMed
  20. Australas Phys Eng Sci Med. 2009 Dec;32(4):180-7 - PubMed
  21. Curr Drug Targets. 2010 Dec;11(12):1517-31 - PubMed
  22. Mediators Inflamm. 1998;7(5):313-7 - PubMed
  23. Ann N Y Acad Sci. 2008 Dec;1147:61-9 - PubMed
  24. Int J Cancer. 2008 May 15;122(10):2360-7 - PubMed
  25. Epidemiology. 2005 Nov;16(6):751-9 - PubMed
  26. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5510-4 - PubMed
  27. Toxicol Appl Pharmacol. 2010 Apr 1;244(1):66-76 - PubMed
  28. Biochem Biophys Res Commun. 1997 Jul 18;236(2):313-22 - PubMed
  29. Methods Enzymol. 2005;401:379-407 - PubMed
  30. Antioxid Redox Signal. 2009 Nov;11(11):2655-71 - PubMed
  31. Mol Neurobiol. 2011 Oct;44(2):192-201 - PubMed
  32. Haematologica. 1990 Nov-Dec;75(6):510-5 - PubMed
  33. Blood. 2005 Jan 15;105(2):659-69 - PubMed
  34. Annu Rev Physiol. 1986;48:721-31 - PubMed
  35. Mol Aspects Med. 2003 Aug-Oct;24(4-5):177-87 - PubMed
  36. Free Radic Biol Med. 1995 Dec;19(6):935-41 - PubMed
  37. Methods Enzymol. 1994;234:279-93 - PubMed
  38. Science. 2004 Jul 16;305(5682):390-2 - PubMed
  39. N Engl J Med. 2009 Mar 12;360(11):1085-95 - PubMed
  40. Biochem Biophys Res Commun. 1976 Feb 23;68(4):1256-62 - PubMed
  41. Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):16912-7 - PubMed
  42. Free Radic Biol Med. 2005 Aug 1;39(3):355-64 - PubMed
  43. Annu Rev Immunol. 2009;27:591-619 - PubMed
  44. J Biol Chem. 1999 Apr 23;274(17):11611-8 - PubMed
  45. Neuromolecular Med. 2008;10(4):236-46 - PubMed
  46. Crit Care Med. 2002 Jan;30(1 Suppl):S12-7 - PubMed
  47. Free Radic Biol Med. 2010 Jan 15;48(2):240-54 - PubMed
  48. J Immunol. 2005 Nov 15;175(10):6968-75 - PubMed
  49. Clin Microbiol Infect. 1998 Jan;4(11):667-669 - PubMed
  50. J Biol Chem. 2006 Nov 3;281(44):33761-72 - PubMed
  51. Circ Res. 2009 Aug 14;105(4):365-74 - PubMed
  52. Endothelium. 2002;9(4):231-8 - PubMed
  53. Biochem Pharmacol. 2008 Dec 1;76(11):1485-9 - PubMed
  54. Proc Soc Exp Biol Med. 1967 Nov;126(2):356-8 - PubMed
  55. FEBS Lett. 2005 Nov 21;579(28):6444-50 - PubMed
  56. Int J Biol Macromol. 2007 Dec 1;41(5):504-11 - PubMed
  57. Toxicol Appl Pharmacol. 2006 Nov 1;216(3):493-504 - PubMed
  58. Arch Med Res. 2006 May;37(4):425-35 - PubMed
  59. Free Radic Biol Med. 1998 Mar 15;24(5):789-97 - PubMed
  60. J Clin Biochem Nutr. 2009 Jan;44(1):1-13 - PubMed
  61. Free Radic Biol Med. 2005 Dec 15;39(12):1629-37 - PubMed
  62. Mol Aspects Med. 2003 Aug-Oct;24(4-5):149-59 - PubMed
  63. Nihon Rinsho Meneki Gakkai Kaishi. 2010;33(5):249-61 - PubMed
  64. Mediators Inflamm. 2007;2007:26785 - PubMed
  65. Toxicol Sci. 2007 Jul;98(1):298-309 - PubMed
  66. Lymphokine Cytokine Res. 1993 Apr;12(2):121-6 - PubMed
  67. Free Radic Biol Med. 1990;9(3):245-65 - PubMed
  68. Free Radic Res. 2010 Nov;44(11):1267-88 - PubMed
  69. Mol Aspects Med. 2003 Aug-Oct;24(4-5):189-94 - PubMed
  70. Mol Aspects Med. 2003 Aug-Oct;24(4-5):167-75 - PubMed
  71. J Appl Physiol (1985). 1995 Nov;79(5):1615-28 - PubMed
  72. Biofactors. 2005;24(1-4):229-36 - PubMed
  73. Free Radic Biol Med. 2011 May 15;50(10):1314-23 - PubMed
  74. Cancer Res. 2006 Aug 15;66(16):8293-6 - PubMed
  75. Int J Toxicol. 2010 Mar-Apr;29(2):165-74 - PubMed
  76. Free Radic Res. 2004 May;38(5):509-16 - PubMed
  77. Diabetes Metab Syndr. 2011 Jan-Mar;5(1):45-9 - PubMed
  78. J Appl Physiol (1985). 2007 Oct;103(4):1189-95 - PubMed
  79. Eur J Appl Physiol Occup Physiol. 1999 Nov-Dec;80(6):549-54 - PubMed
  80. Science. 2002 Dec 13;298(5601):2195-9 - PubMed
  81. Expert Opin Ther Targets. 2009 Jul;13(7):785-94 - PubMed
  82. Front Biosci. 2008 Jan 01;13:2875-87 - PubMed
  83. J Pharmacol Exp Ther. 2005 Jan;312(1):256-64 - PubMed
  84. J Transl Med. 2011 May 17;9:66 - PubMed
  85. Neurochem Res. 2007 Apr-May;32(4-5):931-46 - PubMed
  86. Free Radic Biol Med. 2004 Mar 1;36(5):673-81 - PubMed
  87. Planta Med. 2008 Oct;74(13):1548-59 - PubMed
  88. J Toxicol Environ Health A. 2000 Feb 25;59(4):211-28 - PubMed
  89. Free Radic Res. 1998 Jun;28(6):553-60 - PubMed
  90. J Biol Chem. 2001 Nov 2;276(44):41213-23 - PubMed
  91. Pharmacol Rev. 1991 Jun;43(2):109-42 - PubMed
  92. Hum Exp Toxicol. 2010 Apr;29(4):249-61 - PubMed
  93. Free Radic Biol Med. 2010 Dec 1;49(11):1603-16 - PubMed
  94. J Appl Microbiol. 2009 May;106(5):1715-21 - PubMed
  95. IUBMB Life. 2000 Oct-Nov;50(4-5):315-21 - PubMed
  96. Eur J Pharmacol. 2005 Oct 31;523(1-3):151-61 - PubMed
  97. Med Hypotheses. 1996 Feb;46(2):150-4 - PubMed
  98. JAPCA. 1989 May;39(5):672-95 - PubMed
  99. Am Rev Respir Dis. 1993 Nov;148(5):1363-72 - PubMed
  100. Free Radic Res. 2000 Dec;33(6):795-800 - PubMed
  101. J Am Coll Cardiol. 2008 Sep 16;52(12):971-8 - PubMed
  102. Br J Dermatol. 2005 Dec;153(6):1096-100 - PubMed
  103. Trends Mol Med. 2004 Nov;10(11):549-57 - PubMed
  104. Curr Aging Sci. 2010 Dec;3(3):177-87 - PubMed
  105. Free Radic Biol Med. 1991;11(1):81-128 - PubMed
  106. Free Radic Biol Med. 2006 Jul 15;41(2):302-10 - PubMed
  107. Am J Cardiovasc Drugs. 2011;11(2):73-82 - PubMed
  108. Med Gas Res. 2011 Apr 28;1(1):6 - PubMed
  109. Circulation. 2005 Feb 8;111(5):563-9 - PubMed
  110. Parkinsons Dis. 2011 Feb 22;2011:314082 - PubMed
  111. Free Radic Biol Med. 2002 Feb 15;32(4):360-9 - PubMed
  112. Inflamm Allergy Drug Targets. 2008 Mar;7(1):35-40 - PubMed
  113. PLoS One. 2011 Jan 04;6(1):e14485 - PubMed
  114. Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2027-34 - PubMed
  115. Diabetol Metab Syndr. 2010 May 13;2(1):29 - PubMed
  116. Mol Cell Biochem. 2011 Aug;354(1-2):97-112 - PubMed
  117. Free Radic Biol Med. 2001 Mar 15;30(6):699-706 - PubMed
  118. Recent Pat Antiinfect Drug Discov. 2009 Jun;4(2):130-42 - PubMed
  119. Mediators Inflamm. 2010;2010:610418 - PubMed
  120. Oncogene. 2011 Feb 3;30(5):505-20 - PubMed
  121. Dig Dis Sci. 2001 Nov;46(11):2515-20 - PubMed
  122. Med Res Rev. 2009 Jul;29(4):646-82 - PubMed

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