The rectal insufflation of a judicious dose of ozone, selected from that used in clinical practice, is able to promote oxidative preconditioning or oxidative stress tolerance preventing the hepatocellular damage mediated by free radicals. In order to evaluate the effects of ozone oxidative preconditioning on carbon tetrachloride-mediated hepatotoxicity, the following experimental protocol was designed: group 1 (negative control, sunflower oil i.p.); group 2 (CCl(4) in sunflower oil, 1 ml kg(-1) i.p.); group 3 (15 ozone-oxygen pretreatments at a dose of 1 mg kg(-1) via rectal insufflation + CCl(4) as in group 2); group 4 (ozone control group, 15 ozone-oxygen pretreatments + sunflower oil i.p.). Ozone pretreatment prevented glycogen depletion (as demonstrated by biochemical and histopathological findings) and avoided lactate overproduction associated with the hepatotoxic effects of CCl(4). The administration of CCl(4) increased lipid peroxidation (as measured by thiobarbituric acid-reactive substances) and uric acid levels and inhibited superoxide dismutase activity. All these deleterious effects induced by CCl(4) were prevented by ozone pretreatment. The administration of ozone without CCl(4) (ozone control group) did not produce any changes in the evaluated parameters. Our results showed that ozone treatment, in our experimental conditions, was able to prevent anaerobic glycolysis and oxidative stress induced by CCl(4).
Proteins are major target for radicals and other oxidants when these are formed in both intra- and extracellular environments in vivo. Formation of lesions on proteins may be highly sensitive protein-based biomarkers for oxidative damage in mammalian systems. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. ROS scavenging activities of intact proteins are weaker than those of misfolded proteins or equivalent concentrations of their constituent amino acids. Protein oxidation and enhanced proteolytic degradation, therefore, have been suggested to cause a net increase in ROS scavenging capacity. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, may contribute to the observed accumulation and damaging actions of oxidized proteins during ageing and in pathologies such as diabetes, arteriosclerosis and neurodegenerative diseases. Protein oxidation may play a controlling role in cellular remodelling and cell growth. There is some evidence that antioxidant supplementation may protect against protein oxidation, but additional controlled studies of antioxidant intake to evaluate the significance of dietary/pharmacological antioxidants in preventing physiological/pathological oxidative changes are needed.
Redox environment involves a broad network of pro-oxidant and antioxidant components. Health benefit or damage can be induced as a consequence of an adaptive cellular stress response. A consequence of hormetic amplification is an increase in the homeodynamic space of a living system in terms of an increased defense capacity and a reduced load of damaged macromolecules. Ozone, when used at appropriate doses, promotes the formation of reactive oxygen species and lipid peroxides allows them to become late and long-lasting messengers. Healthy aging may be achieved by hormesis through mild and periodic, but not severe or chronic, physical and mental challenges, and by the use of nutritional hormesis incorporating mild stress-inducing molecules called hormetins. The paradoxical concept that ozone eventually induces an antioxidant response capable of reversing a chronic oxidative stress is common in the animal and vegetal kingdom; it is already supported by findings of an increased level of antioxidant enzymes during ozone therapy. Those facts can include ozone as a hormetin. The established scientific foundations of hormesis are ready to pave the way for new and effective approaches in redox-related disease research and intervention; ozone therapy can be a good candidate.
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