Changes in Oxidative Stress Parameters and Its Correction Opportunities in Particular Pathologies. Summary of the Doctoral Thesis

Abstract

The doctoral thesis deals with two topical global problems – type 2 diabetes and a long-term impact of low doses of ionizing radiation on the body. Oxidative stress is one of the factors contributing to the diabetes complications and postradiation effects, i.e. when antioxidative defence system is unable to sufficiently eliminate damage of lipids, proteins and nucleotides due to reactive oxygen species. The discovery of involvement of the reactive oxygen species (ROS) in the development of cancer, cardiovascular and autoimmune diseases, neurodegenerative disorders, aging and other processes, as well as numerous epidemiological studies in relation to reduction of disease risk using antioxidant-rich products, allowed speaking about a new turning point in medical science. The cell reaction to oxidative stress is an adaptive response of activating mechanisms of reparation, or in case of serious damage – cell death is induced. Thus, the enhanced formation of ROS and insufficient efficiency of antioxidative system lead to oxidative stress, which further contributes to the development of pathological processes. There is evidence that the ROS take part in diabetogenesis and diabetic complications in various organ systems. The body cells of people who have been exposed to ionizing radiation are also damaged by the radiation-induced ROS. Ionizing radiation creates not only direct damage to the structures, but also has a long-term effects on the body, mostly by increasing the risk of cancer, including prostate, diabetes and other diseases related to ROS. The use of antioxidant therapy is currently being considered as a prospective approach to treat patients with the disease in which one of the pathogenic factors is oxidative stress. The reduction of oxidative stress using antioxidants as regulatory mechanisms is an important factor in reducing the genesis of diabetes and development of further complications, as well as post-effect of ionizing radiation. In order to effectively carry out pharmacological intervention using antioxidants, it is important to explore the molecular mechanisms of the damage caused by ROS. Despite the variety of methods available to measure the ROS, currently there are no standardized methods for evaluation of oxidative stress. There are no set guidelines regarding the remedies with antioxidative potency, the time of their administration, dose, and pharmacokinetic studies in critically ill people. There is still a lot of confusion regarding the biological effect of ionizing radiation on the body. The contradictory data obtained in clinical trials can be explained by the fact that there was used a variety of preparations, in different doses, time of administration and route (per os, topical, drops or applications / patches, inhalation or injections), different population and the number of samples. The experimental models show that antioxidants protect against oncogenic transformation caused by radiation, which did not show the same effect in human studies. Since pro-oxidant and antioxidant balance is regulated by a number of metabolic processes, it is virtually impossible to find a universal tool, which could radically change the situation, therefore there must be chosen and combined a number of antioxidants with different modes of action, both water and lipid soluble. Given study has the following aims: 1) to study the oxidative stress adjustment possibilities in the body, using: a) non-steroidal anti-inflammatory drug - Ibuprofen in combination with hydrophilic and lipophilic antioxidants in persons who have received a low-dose ionizing radiation taking part in Chernobyl clean-up work; b) polyphenol containing preparations in 2TD patients; 2) to determine the changes in oxidative stress parameter differences in the patients of Chernobyl clean-up workers with / without 2TD and 2TD who were not exposed to low-dose ionizing radiation. The objectives of the work comprise: 1) the study of the importance of changes in the main oxidative stress indicators in Chernobyl clean-up workers, and evaluation of non-steroidal anti-inflammatory drug- impact of Ibuprofen use in combination with antioxidants - vitamin E and Se in 12 month period (Study I); Se and Coenzyme Q10 (six month period) – on the level of oxidative stress changes (Study II); 2) the changes in 2TCD patients’ oxidative stress indicators and to evaluate efficiency of different doses of natural polyphenols-containing preparations – Ginkgo biloba standardized leave extract; green tea standardized leave extract, and combination preparation Grinvitals Cereloba® plus as a supplement to the standard therapy in relation to changes in oxidative stress parameters (Study III); 3) to study the difference in oxidative stress parameter changes in CNNP clean-up workers with / without T2D and T2D patients who were not exposed to low dose ionizing radiation (Study IV). The results of study I showed that Ibuprofen in combination with antioxidants – vitamin E and Se, in a 12-month period had reliable impact on OS performance gradually reaching their normalization at the end of the study. At the same time, the correlative relation between antioxidants and prooxidants showed preservation of oxidative stress in Chernobyl clean-up workers. Study II showed that Ibuprofen in combination with antioxidants – CoQ10 and Se in six months’ period regulated the body’s antioxidative defence system and the activity of antiradical and antiperoxidative enzyme and increased the amount of nonenzymatic antioxidant, and hampered lipid peroxidation. Results of study III study showed that use of high doses of Ginkgo biloba leave standardized extract over 18 month period had the greatest effect on oxidative stress indicators in 2TD patients compared with applied standard therapy. Study IV showed that changes in the antioxidative system and oxidative stress parameters in Chernobyl clean-up workers with 2TD are less pronounced due to the adaptation to oxidative stress conditions, than in 2TD patients who were not exposed to low doses of ionizing radiation, but higher than in Chernobyl clean-up workers without 2TD and the control groups. Overall, the study results proved the presence of oxidative stress in the body of both 2TD patients and the Chernobyl clean-up workers, which supported the necessity of antioxidants intervention to adjust its level. The results of the doctoral thesis confirm that antioxidants intervention increased antioxidative potency, which allowed adjusting the oxidative stress indicators in case of aftereffects of exposure to ionizing radiation and 2TD. Thus, different duration and different antioxidants combination use together with the basic therapy would allow to significantly improving the health of patients by inhibiting the progression of the disease.