Ozone acting on human blood yields a hormetic dose-response relationship

Journal of Translational Medicine

Volumn 9, Issue , 2011, Pages

  Bocci, Velio A ^a   Zanardi, Iacopo ^a   Travagli, Valter ^a  

^a UNIVERSITY OF SIENA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

OZONE; POLYUNSATURATED FATTY ACID; PROSTACYCLIN; OXIDIZING AGENT;

AUTOIMMUNE DISEASE; BLOOD AUTOTRANSFUSION; BLOOD COMPONENT; CONCENTRATION RESPONSE; DISEASE ASSOCIATION; ERYTHROCYTE; HUMAN; KIDNEY FAILURE; LIPID PEROXIDATION; METABOLIC SYNDROME X; NEUROPATHY; OXIDATIVE STRESS; OZONATION; OZONE THERAPY; PATIENT SAFETY; PERIPHERAL OCCLUSIVE ARTERY DISEASE; PLEIOTROPY; REVIEW; THERAPY EFFECT; THROMBOCYTE; TREATMENT RESPONSE; ARTICLE; BLOOD; BLOOD CELL; DOSE RESPONSE; DRUG EFFECT; METABOLISM;

BLOOD; BLOOD CELLS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; OXIDANTS; OXIDATIVE STRESS; OZONE;

EID: 79955955583     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/1479-5876-9-66     Document Type: Review

References (95)

1. Xia L, Lenaghan SC, Zhang M, Zhang Z, Li Q. Naturally occurring nanoparticles from English ivy: an alternative to metal-based nanoparticles for UV protection. J Nanobiotechnology 2010, 8:12. 10.1186/1477-3155-8-12, 2893082, 20534157.
2. Bell ML, McDermott A, Zeger SL, Samet JM, Dominici F. Ozone and short-term mortality in 95 US urban communities, 1987-2000. JAMA 2004, 292(19):2372-2378. 10.1001/jama.292.19.2372, 15547165.
3. Jerrett M, Burnett RT, Pope CA, Ito K, Thurston G, Krewski D, Shi Y, Calle E, Thun M. Long-term ozone exposure and mortality. N Engl J Med 2009, 360(11):1085-1095. 10.1056/NEJMoa0803894, 19279340.
4. Bocci V, Borrelli E, Travagli V, Zanardi I. The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev 2009, 29(4):646-682. 10.1002/med.20150, 19260079.
5. Bocci V, Di Paolo N. Oxygen-ozone therapy in medicine: an update. Blood Purif 2009, 28(4):373-376. 10.1159/000236365, 19752547.
6. Guven A, Gundogdu G, Vurucu S, Uysal B, Oztas E, Ozturk H, Korkmaz A. Medical ozone therapy reduces oxidative stress and intestinal damage in an experimental model of necrotizing enterocolitis in neonatal rats. J Pediatr Surg 2009, 44(9):1730-1735. 10.1016/j.jpedsurg.2009.01.007, 19735816.
7. Morsy MD, Hassan WN, Zalat SI. Improvement of renal oxidative stress markers after ozone administration in diabetic nephropathy in rats. Diabetol Metab Syndr 2010, 13(2(1)):29.
8. Steppan J, Meaders T, Muto M, Murphy KJ. A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs. J Vasc Interv Radiol 2010, 21(4):534-548. 10.1016/j.jvir.2009.12.393, 20188591.
9. Demirbag S, Uysal B, Guven A, Cayci T, Ozler M, Ozcan A, Kaldirim U, Surer I, Korkmaz A. Effects of medical ozone therapy on acetaminophen-induced nephrotoxicity in rats. Ren Fail 2010, 32(4):493-497. 10.3109/08860221003646352, 20446790.
10. Uysal B, Yasar M, Ersoz N, Coskun O, Kilic A, Cayc T, Kurt B, Oter S, Korkmaz A, Guven A. Efficacy of hyperbaric oxygen therapy and medical ozone therapy in experimental acute necrotizing pancreatitis. Pancreas 2010, 39(1):9-15. 10.1097/MPA.0b013e3181bb5ae3, 19823101.
11. Di Filippo C, Luongo M, Marfella R, Ferraraccio F, Lettieri B, Capuano A, Rossi F, D'Amico M. Oxygen/ozone protects the heart from acute myocardial infarction through local increase of eNOS activity and endothelial progenitor cells recruitment. Naunyn Schmiedebergs Arch Pharmacol 2010, 382(3):287-291. 10.1007/s00210-010-0545-2, 20694792.
12. Timbrell J. The poison paradox: chemicals as friends and foes 2005, New York: Oxford University Press.
13. Olivieri G, Bodycote J, Wolff S. Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 1984, 223(4636):594-597. 10.1126/science.6695170, 6695170.
14. Wolff S. Aspects of the adaptive response to very low doses of radiation and other agents. Mutat Res 1996, 358(2):135-142.
15. Goldman M. Cancer risk of low-level exposure. Science 1996, 271(5257):1821-1822. 10.1126/science.271.5257.1821, 8596947.
16. Calabrese EJ, Baldwin LA. A general classification of U-shaped dose-response relationships in toxicology and their mechanistic foundations. Hum Exp Toxicol 1998, 17(7):353-364. 10.1191/096032798678908918, 9726531.
17. Calabrese EJ, Baldwin LA. Defining hormesis. Hum Exp Toxicol 2002, 21(2):91-97. 10.1191/0960327102ht217oa, 12102503.
18. Calabrese EJ. Hormesis: principles and applications for pharmacology and toxicology. Am J Pharm Toxicol 2008, 3(1):56-68.
19. Calabrese EJ. Hormesis is central to toxicology, pharmacology and risk assessment. Hum Exp Toxicol 2010 29(4):249-261.
20. Bocci V. Oxygen-Ozone Therapy: A Critical Evaluation 2002, Dordrecht, The Netherlands: Kluwer Academic Publisher.
21. Bocci V. Is it true that ozone is always toxic? The end of a dogma. Toxicol Appl Pharmacol 2006, 216(3):493-504. 10.1016/j.taap.2006.06.009, 16890971.
22. Bocci V. The case for oxygen-ozonetherapy. Br J Biomed Sci 2007, 64(1):44-49.
23. Re L. La terapia con ossigeno-ozono o ozormesi: recenti acquisizioni scientifiche. Medici & Medici 2008, 16:18-20.
24. Horvath M, Bilitzky L, Huttner J. Ozone 1985, New York: Elsevier.
25. Wolff HH. Das medizinische Ozon. Theoretische Grundlagen, therapeutische Anwendungen 1998, Heidelberg: Verlag für Medizin Fischer.
26. Bocci V. Ozone. A new medical drug 2011, Dordrecht, The Netherlands: Springer.
27. Aldini G, Gamberoni L, Orioli M, Beretta G, Regazzoni L, Maffei Facino R, Carini M. Mass spectrometric characterization of covalent modification of human serum albumin by 4-hydroxy-trans-2-nonenal. J Mass Spectrom 2006, 41(9):1149-1161. 10.1002/jms.1067, 16888752.
28. Aldini G, Vistoli G, Regazzoni L, Gamberoni L, Facino RM, Yamaguchi S, Uchida K, Carini M. Albumin is the main nucleophilic target of human plasma: a protective role against pro-atherogenic electrophilic reactive carbonyl species?. Chem Res Toxicol 2008, 21(4):824-835. 10.1021/tx700349r, 18324789.
29. Bocci V. Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res 2006, 37(4):425-435. 10.1016/j.arcmed.2005.08.006, 16624639.
30. Shinriki N, Suzuki T, Takama K, Fukunaga K, Ohgiya S, Kubota K, Miura T. Susceptibilities of plasma antioxidants and erythrocyte constituents to low levels of ozone. Haematologia (Budap) 1998, 29(3):229-239.
31. Poli G, Schaur RJ, Siems WG, Leonarduzzi G. 4-Hydroxynonenal: A membrane lipid oxidation product of medicinal interest. Med Res Rev 2008, 28(4):569-631. 10.1002/med.20117, 18058921.
32. Guichardant M, Bacot S, Molière P, Lagarde M. Hydroxy-alkenals from the peroxidation of n-3 and n-6 fatty acids and urinary metabolites. Prostaglandins Leukot Essent Fatty Acids 2006, 75(3):179-182. 10.1016/j.plefa.2006.05.006, 16828271.
33. Long EK, Picklo MJ. Trans-4-hydroxy-2-hexenal, a product of n-3 fatty acid peroxidation: Make some room HNE... Free Radic Biol Med 2010, 49(1):1-8. 10.1016/j.freeradbiomed.2010.03.015, 20353821.
34. Bocci V, Valacchi G, Corradeschi F, Fanetti G. Studies on the biological effects of ozone: 8. Effects on the total antioxidant status and on interleukin-8 production. Mediators Inflamm 1998, 7(5):313-317. 10.1080/09629359890820, 1781866, 9883965.
35. Valacchi G, Bocci V. Studies on the biological effects of ozone: 11. Release of factors from human endothelial cells. Mediators Inflamm 2000, 9(6):271-276. 10.1080/09629350020027573, 1781775, 11213910.
36. Antunes F, Cadenas E. Estimation of H2O2 gradients across biomembranes. FEBS Lett 2000, 475(2):121-126. 10.1016/S0014-5793(00)01638-0, 10858501.
37. Stone JR, Collins T. The role of hydrogen peroxide in endothelial proliferative responses. Endothelium 2002, 9(4):231-238. 10.1080/10623320214733, 12572854.
38. Bocci V, Aldinucci C. Biochemical modifications induced in human blood by oxygenation-ozonation. J Biochem Mol Toxicol 2006, 20(3):133-138. 10.1002/jbt.20124, 16788956.
39. Stone JR, Yang S. Hydrogen peroxide: A signaling messenger. Antioxid Redox Signal 2006, 8(3-4):243-70. 10.1089/ars.2006.8.243, 16677071.
40. Mendiratta S, Qu ZC, May JM. Erythrocyte ascorbate recycling: Antioxidant effects in blood. Free Radic Biol Med 1998, 24(5):789-797. 10.1016/S0891-5849(97)00351-1, 9586809.
41. Bocci V, Luzzi E, Corradeschi F, Paulesu L, Rossi R, Cardaioli E, Di Simplicio P. Studies on the biological effects of ozone: 4. Cytokine production and glutathione levels in human erythrocytes. J Biol Regul Homeost Agents 1993, 7(4):133-138.
42. Packer L, Roy S, Sen CK. Alpha-lipoic acid: A metabolic antioxidant and potential redox modulator of transcription. Adv Pharmacol 1997, 38:79-101.
43. Rokitanski O, Rokitanski A, Steiner J, Trubel W, Viebahn R, Washüttl J. Die ozontherapie bei peripheren, arteriellen Durchblutungs-strörugen; klinik, biochemische und blutgasanalytische untersuchungen. Wasser IOA 1981, 53-75. Ozon-Weltkongress: Berlin.
44. Bocci V, Larini A, Micheli V. Restoration of normoxia by ozone therapy may control neoplastic growth: a review and a working hypothesis. J Altern Complement Med 2005, 11(2):257-265. 10.1089/acm.2005.11.257, 15865491.
45. Babior BM, Takeuchi C, Ruedi J, Gutierrez A, Wentworth P. Investigating antibody-catalyzed ozone generation by human neutrophils. Proc Natl Acad Sci USA 2003, 100(6):3031-3034. 10.1073/pnas.0530251100, 152239, 12601145.
46. Shin HW, Umber BJ, Meinardi S, Leu SY, Zaldivar F, Blake DR, Cooper DM. Acetaldehyde and hexanaldehyde from cultured white cells. J Transl Med 2009, 7:31. 10.1186/1479-5876-7-31, 2683805, 19402909.
47. Volkhovskaya NB, Tkachenko SB, Belopolsky AA. Modulation of phagocytic activity of blood polynuclear leukocytes with ozonized physiological saline. Bull Exp Biol Med 2008, 146(5):559-561. 10.1007/s10517-009-0340-6, 19526090.
48. Sen R, Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell 1986, 47(6):921-928. 10.1016/0092-8674(86)90807-X, 3096580.
49. Baeuerle PA, Henkel T. Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 1994, 12:141-79. 10.1146/annurev.iy.12.040194.001041, 8011280.
50. Bocci V, Paulesu L. Studies on the biological effects of ozone 1. Induction of interferon gamma on human leucocytes. Haematologica 1990, 75(6):510-515.
51. Burgassi S, Zanardi I, Travagli V, Montomoli E, Bocci V. How much ozone bactericidal activity is compromised by plasma components?. J Appl Microbiol 2009, 106(5):1715-1721. 10.1111/j.1365-2672.2008.04141.x, 19226394.
52. Valacchi G, Bocci V. Studies on the biological effects of ozone: 10. Release of factors from ozonated human platelets. Mediators Inflamm 1999, 8(4-5):205-9. 10.1080/09629359990360, 1781810, 10704074.
53. Petersen DR, Doorn JA. Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radic Biol Med 2004, 37(7):937-945. 10.1016/j.freeradbiomed.2004.06.012, 15336309.
54. Bocci V, Valacchi G, Corradeschi F, Aldinucci C, Silvestri S, Paccagnini E, Gerli R. Studies on the biological effects of ozone: 7. Generation of reactive oxygen species (ROS) after exposure of human blood to ozone. J Biol Regul Homeost Agents 1998, 12(3):67-75.
55. Siems W, Grune T. Intracellular metabolism of 4-hydroxynonenal. Mol Aspects Med 2003, 24(4-5):167-175. 10.1016/S0098-2997(03)00011-6, 12892994.
56. Awasthi YC, Ansari GA, Awasthi S. Regulation of 4-hydroxynonenal mediated signaling by glutathione S-transferase. Methods Enzymol 2005, 401:379-407.
57. Petras T, Siems W, Grune T. 4-Hydroxynonenal is degraded to mercapturic acid conjugate in rat kidney. Free Radic Biol Med 1995, 19(5):685-688. 10.1016/0891-5849(95)00060-B, 8529929.
58. Alary J, Geuraud F, Cravedi JP. Fate of 4-hydroxynonenal in vivo: Disposition and metabolic pathways. Mol Aspects Med 2003, 24(4-5):177-187. 10.1016/S0098-2997(03)00012-8, 12892995.
59. Jardines D, Correa T, Ledea O, Zamora Z, Rosado A, Molerio J. Gas chromatography-mass spectrometry profile of urinary organic acids of Wistar rats orally treated with ozonized unsaturated triglycerides and ozonized sunflower oil. J Chromatogr B Analyt Technol Biomed Life Sci 2003, 783(2):517-525. 10.1016/S1570-0232(02)00707-9, 12482495.
60. Bocci V. Does ozone therapy normalize the cellular redox balance? Implications for therapy of human immunodeficiency virus infection and several other diseases. Med Hypotheses 1996, 46(2):150-154. 10.1016/S0306-9877(96)90016-X, 8692040.
61. Takahashi K, Hara E, Ogawa K, Kimura D, Fujita H, Shibahara S. Possible implications of the induction of human heme oxygenase-1 by nitric oxide donors. J Biochem 1997, 121(6):1162-1168.
62. Dianzani MU. 4-Hydroxynonenal and cell signalling. Free Radic Res 1998, 28(6):553-560. 10.3109/10715769809065811, 9736307.
63. Lin F, Josephs SF, Alexandrescu DT, Ramos F, Bogin V, Gammill V, Dasanu CA, De Necochea-Campion R, Patel AN, Carrier E, Koos DR. Lasers, stem cells, and COPD. J Transl Med 2010, 8:16. 10.1186/1479-5876-8-16, 2830167, 20158898.
64. Bocci V, Aldinucci C, Mosci F, Carraro F, Valacchi G. Ozonation of human blood induces a remarkable upregulation of heme oxygenase-1 and heat stress protein-70. Mediators Inflamm 2007, 2007:26785. 2233812, 18274635.
65. Chaudhary P, Sharma R, Sharma A, Vatsyayan R, Yadav S, Singhal SS, Rauniyar N, Prokai L, Awasthi S, Awasthi YC. Mechanisms of 4-hydroxy-2-nonenal induced pro- and anti-apoptotic signaling. Biochemistry 2010 49(29):6263-6275.
66. Taha H, Skrzypek K, Guevara I, Nigisch A, Mustafa S, Grochot-Przeczek A, Ferdek P, Was H, Kotlinowski J, Kozakowska M, Balcerczyk A, Muchova L, Vitek L, Weigel G, Dulak J, Jozkowicz A. Role of heme oxygenase-1 in human endothelial cells: lesson from the promoter allelic variants. Arterioscler Thromb Vasc Biol 2010, 30(8):1634-1641. 10.1161/ATVBAHA.110.207316, 2906705, 20508205.
67. Wang R. Two's company, three's a crowd: can H2S be the third endogenous gaseous transmitter?. FASEB J 2002, 16(13):1792-1798. 10.1096/fj.02-0211hyp, 12409322.
68. Nakao A, Sugimoto R, Billiar TR, McCurry KR. Therapeutic antioxidant medical gas. J Clin Biochem Nutr 2009, 44(1):1-13. 10.3164/jcbn.08-193R, 2613492, 19177183.
69. Calabrese EJ, Stanek EJ, Nascarella MA, Hoffmann GR. Hormesis predicts low-dose responses better than threshold models. Int J Toxicol 2008, 27(5):369-378. 10.1080/10915810802503735, 19037807.
70. Bocci V, Zanardi I, Travagli V. Potentiality of oxygen-ozone therapy to improve the health of aging people. Curr Aging Sci 2010, 3(3):177-187. 10.2174/1874609811003030177, 20735348.
71. Michaud K, Matheson K, Kelly O, Anisman H. Impact of stressors in a natural context on release of cortisol in healthy adult humans: a meta-analysis. Stress 2008, 11(3):177-197. 10.1080/10253890701727874, 18465466.
72. Viru A, Tendzegolskis Z. Plasma endorphin species during dynamic exercise in humans. Clin Physiol 1995, 15(1):73-79.
73. Travagli V, Zanardi I, Silvietti A, Bocci V. A physicochemical investigation on the effects of ozone on blood. Int J Biol Macromol 2007, 41(5):504-511. 10.1016/j.ijbiomac.2007.06.010, 17675149.
74. Travagli V, Zanardi I, Bernini P, Nepi S, Tenori L, Bocci V. Effects of ozone blood treatment on the metabolite profile of human blood. Int J Toxicol 2010, 29(2):165-174. 10.1177/1091581809360069, 20335512.
75. Hunter PE, Krithayakiern V. Effect of gamma radiation upon life expectancy and reproduction in the house cricket, Acheta domesticus (Orthoptera: Gryllidae). Ann. Entomol. Soc. America 1971, 64:119-123.
76. Meng Z. Effects of arsenic on DNA synthesis in human lymphocytes. Arch Environ Contam Toxicol 1993, 25(4):525-528.
77. Tang L, Mamotte CD, Van Bockxmeer FM, Taylor RR. The effect of homocysteine on DNA synthesis in cultured human vascular smooth muscle. Atherosclerosis 1998, 136(1):169-173. 10.1016/S0021-9150(97)00208-6, 9544744.
78. Rattan SIS, Demirovic D. Hormesis and aging. Hormesis: A Revolution in Biology, Toxicology and Medicine 2010, 153-175. Humana Press, Springer Science and Business Media, Mattson MP and Calabrese E. Totowa NJ.
79. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 1999, 26(9-10):1231-1237. 10.1016/S0891-5849(98)00315-3, 10381194.
80. Matassi R, D'Angelo F, Bisetti P, Colombo R, Vaghi M. Terapia con ozono per via parenterale nelle arteriopatie obliteranti periferiche: Meccanismo biochimico e risultati clinici. Il Giornale di Chirurgia 1987, VIII:109-111.
81. Hernández F, Menéndez S, Wong R. Decrease of blood cholesterol and stimulation of antioxidative response in cardiopathy patients treated with endovenous ozone therapy. Free Radic Biol Med 1995, 19(1):115-119. 10.1016/0891-5849(94)00201-T, 7635353.
82. Di Paolo N, Bocci V, Garosi G, Borrelli E, Bravi A, Bruci A, Aldinucci C, Capotondo L. Extracorporeal blood oxygenation and ozonation (EBOO) in man. Preliminary report. Int J Artif Organs 2000, 23(2):131-41.
83. Biedunkiewicz B, Tylicki L, Nieweglowski T, Burakowski S, Rutkowski B. Clinical efficacy of ozonated autohemotherapy in hemodialyzed patients with intermittent claudication: An oxygen-controlled study. Int J Artif Organs 2004, 27(1):29-34.
84. De Monte A, van der Zee H, Bocci V. Major ozonated autohemotherapy in chronic limb ischemia with ulcerations. J Altern Complement Med 2005, 11(2):363-367. 10.1089/acm.2005.11.363, 15865505.
85. Di Paolo N, Bocci V, Salvo DP, Palasciano G, Biagioli M, Meini S, Galli F, Ciari I, Maccari F, Cappelletti F, Di Paolo M, Gaggiotti E. Extracorporeal blood oxygenation and ozonation (EBOO): a controlled trial in patients with peripheral artery disease. Int J Artif Organs 2005, 28(10):1039-1050.
86. Bocci V, Zanardi I, Travagli V. Ozone: A New Therapeutic Agent in Vascular Diseases. Am J Cardiovasc Drugs 2011, 11(2):73-82. 10.2165/11539890-000000000-00000, 21446774.
87. Martínez-Sánchez G, Pérez-Davison G, Re L, Giuliani A. Ozone as U-shaped dose responses molecules (Hormetins). Dose Response 2011, 9(1):32-49.
88. Bocci V, Zanardi I, Huijberts MSP, Travagli V. Diabetes and chronic oxidative stress. A perspective based on the possible usefulness of ozone therapy. Diab Met Syndr: Clin Res Rev 2011, 5(1):45-49.
89. Travagli V, Zanardi I, Valacchi G, Bocci V. Ozone and ozonated oils in skin diseases: a review. Mediators Inflamm 2010, 2010:610418. 2910505, 20671923.
90. Valacchi G, Lim Y, Belmonte G, Miracco C, Zanardi I, Bocci V, Travagli V. Ozonated sesame oil enhances cutaneous wound healing in SKH1 mice. Wound Repair Regen 2011, 19(1):107-115. 10.1111/j.1524-475X.2010.00649.x, 21134039.
91. Galli F. Protein damage and inflammation in uraemia and dialysis patients. Nephrol Dial Transplant 2007, 22(suppl 5):v20-36.
92. Ruggenenti P, Schieppati A, Remuzzi G. Progression, remission, regression of chronic renal diseases. Lancet 2001, 357(9268):1601-1608. 10.1016/S0140-6736(00)04728-0, 11377666.
93. Calunga JL, Trujillo Y, Menéndez S, Zamora Z, Alonso Y, Merino N, Montero T. Ozone oxidative post-conditioning in acute renal failure. J Pharm Pharmacol 2009, 61(2):221-227.
94. Bocci V, Zanardi I, Michaeli D, Travagli V. Mechanisms of action and chemical-biological interactions between ozone and body compartments: a critical appraisal of the different administration routes. Curr Drug Ther 2009, 4(3):159-173.
95. Grocott MP, Martin DS, Levett DZ, McMorrow R, Windsor J, Montgomery HE, . Caudwell Xtreme Everest Research Group Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 2009, 360(2):140-149. 10.1056/NEJMoa0801581, 19129527, Caudwell Xtreme Everest Research Group.