Skip to main content

Advertisement

SpringerLink
Log in

Appraisal of ozone as biologically active molecule and experimental tool in biomedical sciences

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Ozone (O3) (CAS 10028-15-6) is a major air industrial pollutant and is well known for its very strong oxidative actions which affords the molecule its useful antimicrobial and deodorizing properties, but also its potential toxic effects. Knowledge of the activity and safety of ozone is important if its potential for use as a biologically active agent is to be realized, especially in view of the numerous unsubstantiated medicinal claims that are being made. To investigate ozone-induced oxidative stress as a model for investigating the neurobiology and treatment of certain central nervous system disorders, an experimental ozone inhalation model was developed to administer ozone to intact test animals following acute or chronic exposure. The model was successfully utilized to investigate the effect of dose and duration of exposure to ozone and its resultant effect on oxidative stress markers, depressive-like behaviours and response to antidepressant treatment. These studies demonstrate that the model not only is useful for studying the biological activity of ozone, but also for studying disorders of the brain associated with increased oxidative stress as well as the effects of altered redox status on drug treatment and response.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Scheme 1
Fig. 4

Similar content being viewed by others

References

  • Abu-Naba’a L, Shorman HAL, Holmes J, Petersson LG, Tagami J, Lynch E (2004) Evidence-based research into ozone treatment in dentistry: an overview. In: Lynch E (ed) Ozone: the revolution in dentistry. Quintessence Publishing Co. Ltd, Surrey, pp 73–115

    Google Scholar 

  • Alvarez RG, Zamora ZB, Borrego A, Delgado R, Schulz S, Alonso Y (2009) Ozone oxidative preconditioning reduces nitrite levels in blood serum in LPS: induced endotoxic shock in mice. Inflamm Res 58:441–443

    Article  PubMed  CAS  Google Scholar 

  • Avila-Costa MR, Colín-Barenque L, Fortoul TI, Machado-Salas JP, Espinosa-Villanueva J, Rugerio-Vargas C, Rivas-Arancibia S (1999) Memory deterioration in an oxidative stress model and its correlation with cytological changes on rat hippocampus CA1. Neurosci Lett 270:107–109

    Article  PubMed  CAS  Google Scholar 

  • Avila-Costa MR, Colín-Barenque L, Fortoul TI, Machado-Salas JP, Espinosa-Villanueva J, Rugerio-Vargas C, Borgonio G, Dorado C, Rivas-Arancibia S (2001) Motor impairments in an oxidative stress model and its correlation with cytological changes on rat striatum and prefrontal cortex. Int J Neurosci 108:193–200

    Article  PubMed  CAS  Google Scholar 

  • Azarpazhooh A, Limeback H (2008) The application of ozone in dentistry: a systematic review of literature. J Dent 36:104–116

    Article  PubMed  CAS  Google Scholar 

  • Bocci V (1996) Does ozone therapy normalize the cellular redox balance? Implications for the therapy of human immunodeficiency virus infection and several other diseases. Med Hypotheses 46:150–154

    Article  PubMed  CAS  Google Scholar 

  • Bocci VA (2006) Scientific and medical aspects of ozone therapy. State of the art. Arch Med Res 37:425–435

    Article  PubMed  CAS  Google Scholar 

  • Bocci V, Borrelli E, Travagli V, Zanardi I (2009) The ozone paradox: ozone is a strong oxidant as well as a medical drug. Med Res Rev 29:646–682

    Article  PubMed  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Brink CB, Pretorius A, van Niekerk BPJ, Oliver DW, Venter DP (2008) Studies on cellular resilience and adaptation following acute and repetitive exposure to ozone in cultured human epithelial (HeLa) cells. Redox Rep 13:87–100

    Article  PubMed  CAS  Google Scholar 

  • Cataldo F, Gentilini L (2005) Chemical kinetics measurements on the reaction between blood and ozone. Int J Biol Macromol 36:61–65

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Xing B, Liu X, Zhan B, Zhou J, Zhu H, Chen Z (2008a) Ozone oxidative preconditioning protects the rat kidney from reperfusion injury: the role of nitric oxide. J Surg Res 149:287–295

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Xing B, Liu X, Zhan B, Zhou J, Zhu H, Chen Z (2008b) Similarities between ozone oxidative preconditioning and ischemic preconditioning in renal ischemia/reperfusion injury. Arch Med Res 39:169–178

    Article  PubMed  CAS  Google Scholar 

  • Chen H, Xing B, Liu X, Zhan B, Zhou J, Zhu H, Chen Z (2008c) Ozone oxidative preconditioning inhibits inflammation and apoptosis in a rat model of renal ischemia/reperfusion injury. Eur J Pharmacol 581:306–314

    Article  PubMed  CAS  Google Scholar 

  • Chiu K, Lau WM, Lau HT, So KF, Chang RC (2007) Micro-dissection of rat brain for RNA or protein extraction from specific brain region. JoVE 7:269

    PubMed  Google Scholar 

  • Chuang GC, Yang Z, Westbrook DG, Pompilius M, Ballinger CA, White CR, Krzywanski DM, Postlethwait EM, Ballinger SW (2009) Pulmonary ozone exposure induces vascular dysfunction, mitochondrial damage, and atherogenesis. Am J Physiol Lung Cell Mol Physiol 297:L209–L216

    Article  PubMed  CAS  Google Scholar 

  • Colín-Barenque L, Avila-Costa MR, Fortoul T, Rugerio-Vargas C, Machado-Salas JP, Espinosa-Villanueva J, Rivas-Arancibia S (1999) Morphologic alteration of the olfactory bulb after acute ozone exposure in rats. Neurosci Lett 274:1–4

    Article  PubMed  Google Scholar 

  • Cross CE, Reznick AZ, Packer L, Davis PA, Suzuki YJ, Halliwell B (1992) Oxidative damage to human plasma proteins by ozone. Free Radic Res Commun 15:347–352

    Article  PubMed  CAS  Google Scholar 

  • De Monte A, Van Der Zee H, Bocci V (2005) Major ozonated autohemotherapy in chronic limb ischemia with ulcerations. J Altern Complement Med 11:363–367

    Article  PubMed  Google Scholar 

  • Di Paolo N, Gaggiotti E, Galli F (2005) Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy. Redox Rep 10:121–130

    Article  PubMed  Google Scholar 

  • Emberson LD, Büker P, Ashmore MR (2007) Assessing the risk caused by ground level ozone to European forest trees: a case study in pine, beech and oak across different climate regions. Environ Pollut 147:454–466

    Article  PubMed  CAS  Google Scholar 

  • Hackney JD, Linn WS, Buckley RD, Hislop HJ (1976) Studies in adaption to ambient oxidant air pollution: effects of ozone exposure in Los Angeles residents vs. new arrivals. Environ Health Perspect 18:141–146

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Cross CE (1994) Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect 102:5–12

    PubMed  CAS  Google Scholar 

  • Harvey BH (2008) Is major depressive disorder a metabolic encephalopathy? Hum Psychopharmacol 23:371–384

    Article  PubMed  Google Scholar 

  • Harvey BH, Joubert C, Du Preez JL, Berk M (2008) Effect of chronic N-acetyl cysteine administration on oxidative status in the presence and absence of induced oxidative stress in rat striatum. Neurochem Res 33:508–517

    Article  PubMed  CAS  Google Scholar 

  • Holmes J (2003) Clinical reversal of root caries using ozone, double-blind, randomised, controlled 18-month trial. Gerodontology 20:106–114

    Article  PubMed  CAS  Google Scholar 

  • Jacobson JS, Grann VR, Gnatt MA, Hibshoosh H, Austin JHM, Millar WS, Neugut AI (2005) Cancer outcomes at the Hufeland (complementary/alternative medicine) klinik: a best-case series review. Integr Cancer Ther 4:156–167

    Article  PubMed  Google Scholar 

  • Jerrett M, Burnett RT, Arden Pope C III, Ito K, Thurston G, Krewski D, Shi Y, Calle E, Thun M (2009) Long-term ozone exposure and mortality. N Engl J Med 360:1085–1095

    Article  PubMed  CAS  Google Scholar 

  • Kesik V, Uysal B, Kurt B, Kismet E, Koseoglu V (2009) Ozone ameliorates methotrexate-induced intestinal injury in rats. Cancer Biol Ther 8:1623–1628

    Article  PubMed  CAS  Google Scholar 

  • Kowalski WJ, Bahnfleth WP, Striebig BA, Whittam TS (2003) Demonstration of a hermetic airborne ozone disinfection system: studies on E. coli. Am Ind Hyg Assoc J 64:222–227

    Article  CAS  Google Scholar 

  • Kulle TJ, Sauder LR, Hebel JR, Chatham MD (1985) Ozone response relationships in healthy nonsmokers. Am Rev Respir Dis 132:36–41

    PubMed  CAS  Google Scholar 

  • León OS, Menéndez S, Merino N, Castillo R, Sam S, Pérez L, Cruz E, Bocci V (1998) Ozone oxidative preconditioning: a protection against cellular damage by free radicals. Mediat Inflamm 7:289–294

    Article  Google Scholar 

  • Lotriet CJ, Oliver DW, Venter DP (2007) The pharmacological effects of ozone on isolated guinea pig tracheal preparations. Arch Toxicol 81:433–440

    Article  PubMed  CAS  Google Scholar 

  • Lupien SJ, McEwen BS, Gunnar MR, Heim C (2009) Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 10:434–445

    Article  PubMed  CAS  Google Scholar 

  • Ottino P, Duncan JR (1997) Effect of vitamin E succinate on free radical formation, lipid peroxidation levels and cyclooxygenase activity in murine melanoma cells. Nutr Res 17:661–676

    Article  CAS  Google Scholar 

  • Paz C, Huitrón-Reséndiz S (1996) The effects of ozone exposure on the sleep-wake cycle and serotonin contents in the pons of the rat. Neurosci Lett 204:49–52

    Article  PubMed  CAS  Google Scholar 

  • Rivas-Arancibia S, Vazquez-Sandoval R, Gonzalez-Kladiano D, Schneider-Rivas S, Lechuga-Guerrero A (1998) Effects of ozone exposure in rats on memory and levels of brain and pulmonary superoxide dismutase. Environ Res 76:33–39

    Article  PubMed  CAS  Google Scholar 

  • Rivas-Arancibia S, Dorado-Martínez C, Colin-Barenque L, Kendrick KM, De La Riva C, Guevara-Guzmán R (2003) Effect of acute ozone exposure on locomotor behavior and striatal function. Pharmacol Biochem Behav 74:891–900

    Article  PubMed  CAS  Google Scholar 

  • Rodríguez ZZ, Guanche D, Álvarez RG, Rosales FH, Alonso Y and Schulz S (2009) Preconditioning with ozone/oxygen mixture induces reversion of some indicators of oxidative stress and prevents organic damage in rats with fecal peritonitis. Inflamm Res 1–5

  • Shelley SA, Paciga JE, Paterson JF, Balis JU (1989) Ozone-induced alterations of lamellar body lipid and protein during alveolar injury and repair. Lipids 24:769–774

    Article  PubMed  CAS  Google Scholar 

  • South African Bureau of Standards (2004) SANS 1929: 2004. Pretoria

  • Stadlbauer THW, Eisele A, Heidt MC, Tillmanns HH, Schulz S (2008) Preconditioning with ozone abrogates acute rejection and prolongs cardiac allograft survival in rats. Transpl Proc 40:974–977

    Article  CAS  Google Scholar 

  • Stokinger HE (1956) Methods of establishing threshold limits; prepared discussion. Am Ind Hyg Assoc Q 17:284–286

    PubMed  CAS  Google Scholar 

  • Stokinger HE (1965) Ozone toxicology. Arch Environ Health 10:719–731

    PubMed  CAS  Google Scholar 

  • Travagli V, Zanardi I, Bocci V (2006) A realistic evaluation of the action of ozone on whole human blood. Int J Biol Macromol 39:317–320

    Article  PubMed  CAS  Google Scholar 

  • US EPA (2010) Ozone generators that are sold as air cleaners. 3 Feb 2010: http://www.epa.gov/iaq/pubs/ozonegen.html

  • Valacchi G, Fortino V, Bocci V (2005) The dual action of ozone on the skin. Br J Dermatol 153:1096–1100

    Article  PubMed  CAS  Google Scholar 

  • Von Gunten U (2003a) Ozonation of drinking water: part I. Oxidation kinetics and product formation. Water Res 37:1443–1467

    Article  Google Scholar 

  • Von Gunten U (2003b) Ozonation of drinking water: part II. Disinfection and by-product formation in presence of bromide, iodide or chlorine. Water Res 37:1469–1487

    Article  Google Scholar 

  • Werkmeister H (1969) Contribution to the therapy of the so-called reticulosarcomatosis cutis Gottron. Strahlentherapie Sonderband 69:154–159

    CAS  Google Scholar 

  • Zamora ZB, Borrego A, López OY, Delgado R, Menéndez S, Schulz S, Hernández F (2004) Inhibition of tumor necrosis factor-alpha release during endotoxic shock by ozone oxidative preconditioning in mice. Arzneimittel-Forschung/Drug Res 54:906–909

    CAS  Google Scholar 

  • Zamora ZB, Borrego A, López OY, Delgado R, González R, Menéndez S, Hernández F, Schulz S (2005) Effects of ozone oxidative preconditioning on TNF-α release and antioxidant-prooxidant intracellular balance in mice during endotoxic shock. Mediat Inflamm 2005:16–22

    Article  Google Scholar 

Download references

Acknowledgments

The South African National Research Foundation (NRF) (Grant no. 45846) is thanked for financial support.

Author information

Authors and Affiliations

  1. Unit for Drug Research and Development, School of Pharmacy, North-West University, Potchefstroom Campus, Private Bag X6001, Potchefstroom, 2530, South Africa

    Mmalebuso L. Mokoena, Christiaan B. Brink, Brian H. Harvey & Douglas W. Oliver

Authors
  1. Mmalebuso L. Mokoena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christiaan B. Brink
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian H. Harvey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Douglas W. Oliver
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Douglas W. Oliver.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mokoena, M.L., Brink, C.B., Harvey, B.H. et al. Appraisal of ozone as biologically active molecule and experimental tool in biomedical sciences. Med Chem Res 20, 1687–1695 (2011). https://doi.org/10.1007/s00044-010-9493-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-010-9493-0

Keywords

Search

Navigation