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

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

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.

Figures

Figure 1
Figure 1
Cellular responses to oxidant exposure. ROOH and ROO• indicate lipohydroperoxide and its oxygen centered organic radicals formed by radical reactions with cellular components, respectively. GSH and GSSG represent the sulfhydryl/disulfide pair of glutathione species. Nicotinamide adenine dinucleotide phosphate, NADP(H), is the primary electron source, regenerated by the cellular reduction systems.
Figure 2
Figure 2
Generic scheme of polyunsaturated fatty acids peroxidation. Arachidonic acid reactions have been detailed, but similar pathways are applicable to other polyenoic fatty acids. MDA: malondialdehyde. HHE: 4-hydroxy-2E-hexenal. HNE: 4-hydroxy-2E-nonenal.
Figure 3
Figure 3
The hypothetical inverted U-shaped curve describing an ideal dose-response relationship (panel A). The inverted U-shaped curve drawn on the basis of the therapeutic effect in PAD's patients by using an ozone concentration range between 15 and 80 μg/ml of gas per ml of blood. During a course of 15-20 sessions, the initial ozone concentration of 10 μg/ml has been slowly upgraded to the concentration of 80 μg/ml (panel B). The end-points that have been considered to determine the therapeutic effects are: claudication; ankle-brachial index; disappearance of pain; healing of skin ulcers.

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