The effect of blood ozonation on mitochondrial function and apoptosis of peripheral blood mononuclear cells in the presence and absence of plasma antioxidants

Ozone-autohemotherapy (O3-AHT) has recently gained interest as a form of alternative and complementary medicine. There is, however, some concern regarding its toxicity and effectiveness. Ozone is a powerful oxidant and when introduced into biological fluids react with most cellular components including proteins, lipids and DNA. We assessed the effect of O3-AHT on peripheral blood mononuclear cells (PBMC) viability, apoptosis and mitochondrial function in the presence and absence of plasma antioxidants. Exposure to ozone increased lactate dehydrogenase (LDH) release and caspase 3/7 activity in PBMC. A decrease in mitochondrial function was measured as a decrease in ATP levels and an increase in NADH/ NAD+ ratio. Complex IV (cytochrome c oxidase) of the respiratory chain was almost completely inhibited by ozone. These results indicated that the death of PBMC was probably through apoptosis. These effects were more evident in the absence of plasma antioxidants. Therefore, high concentrations of ozone were damaging to the cells, but this effect was diminished by antioxidants present in plasma. It is not certain if the in vitro damage will be propagated when ozonated blood is injected back into individuals. One must bear in mind that only a fraction of the total blood volume is ozonated

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Multiple independent appearances of the cecal appendix in mammalian evolution and an investigation of related ecological and anatomical factors.

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