Ozone acting on human blood yields a hormetic dose-response relationship
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Ozone acting on human blood yields a hormetic dose-response relationship Velio A Bocci1*, Iacopo Zanardi2 and Valter Travagli2*
Abstract The aim of this paper is to analyze why ozone can be medically useful when it dissolves in blood or in other biological fluids. In reviewing a number of clinical studies performed in Peripheral Arterial Diseases (PAD) during the last decades, it has been possible to confirm the long-held view that the inverted U-shaped curve, typical of the hormesis concept, is suitable to represent the therapeutic activity exerted by the so-called ozonated autohemotherapy. The quantitative and qualitative aspects of human blood ozonation have been also critically reviewed in regard to the biological, therapeutic and safety of ozone. It is hoped that this gas, although toxic for the pulmonary system during prolonged inhalation, will be soon recognized as a useful agent in oxidative-stress related diseases, joining other medical gases recently thought to be of therapeutic importance. Finally, the elucidation of the mechanisms of action of ozone as well as the obtained results in PAD may encourage clinical scientists to evaluate ozone therapy in vascular diseases in comparison to the current therapies. Introduction Ozone is a double-faceted gas. It has a crucial protective relevance in partially blocking mutagenic and carcinogenic UV radiations emitted by the sun (wavelengths of 100-280 nm) in the stratosphere [1], while its increasing concentration in the troposphere causes severe pulmonary damage and increased mortality [2,3]. In spite of this drawback, there are growing experimental and clinical evidences about the medical use of ozone [4-11]. Since XVI Century, Paracelsus had ingeniously guessed that “all things are poison and nothing is without poison and only the right dose differentiates a poison from a remedy”. In 2005, Timbrell reiterated the concept in his book: “The poison paradox; chemicals as friends and foes” [12]. During the Earth evolution, harnessing oxygen by metazoans has allowed a fantastic biodiversity and growth but it has also created a slow acting “poison”. It is reasonable to believe that the antioxidant system slowly evolved and specialized during the last two billion years for counteracting the daily formation (3-5 g in humans) of anion superoxide in the mitochondria * Correspondence: [email protected]; [email protected] 1 Dipartimento di Fisiologia, Università degli Studi di Siena, Viale Aldo Moro, 2, 53100, Siena, Italy 2 Dipartimento Farmaco Chimico Tecnologico and European Research Center for Drug Discovery and Development, Università degli Studi di Siena, Viale Aldo Moro, 2, 53100, Siena, Italy Full list of author information is available at the end of the article
and the release of H 2 O 2 by ubiquitous NADPH oxidases. However, there is a general consensus that the physiological production of H 2 O 2 is essential for life. Olivieri et al. [13] and Wolff [14] were the first to describe the effect of either low concentrations of radioactive thymidin
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