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Potassium fenozan and possible mechanisms of its action on the functional status of mitochondria in low and ultra-low dosesтезисы доклада
- Авторы: Zhigacheva I.V., Evseenko L.S., Mokhova E.N.
- Сборник: Abstracts of 2nd International Congress-Partnering and Exhibition on Biotechnology and Bioenergy
- Тезисы
- Год издания: 2010
- Место издания: Moscow, Russia
- Первая страница: 69
- Последняя страница: 70
- Аннотация: In all cells and all their frequent formation of reactive oxygen species (ROS). In a normal steady-state level of ROS in organs and tissues is very low (around 10-10 - 10-11 M) due to the prevalence of these powerful enzymatic and non-enzymatic regulatory systems of accumulation and elimination of ROS. Value pro-oxidants and antioxidants determines, develops, and whether progress oxidative stress and as a result of free radical pathology. Pathological consequences arise when excessive accumulation of ROS and activation of lipid peroxidation (LPO). Generated in mitochondria reactive oxygen species (ROS) can damage not only the mitochondrial biomolecules, such as mitochondrial DNA, but and various intracellular structures. So, creation and research of new antioxidants are related to basic medical problems. The problem of selecting the most effective concentrations of drugs, in particular antioxidants are especially important in view of the fact that many biologically active substances (BAS) have a dose-dependent in the manifestation of its activity (Burlakova EB et al, 2003). The aim of our work was to study the effect of various antioxidant potassium fenozan concentrations on lipid peroxidation in the membranes of mitochondria. Oxidative stress causes long-term storage "aging" of mitochondria (4 mg protein) in 0.5 ml incubation medium (70 mM KCl, 1 KH2PO4, pH 7,4). "Aging" activated LPO. Introduction drug 10-8- 10-16 M and 10-18-10-22M in the incubation medium reduced the intensity of mitochondrial lipid peroxidation to control values. We proposed that fenozan produced its protective effect via different mechanisms within various concentration intervals To elucidation this question the number of fenozan molecules in the sample, and relation between this value and the numbers of mitochondria in each sample were calculated. It is known that 1 M of any substance contains 6.02x1023 molecules in 1 liter. At 10-8 M fenozan concentration, the well contains 3x1012 fenozan molecule. Calculation (according to K. Schwerzmann et al., 1986) shows that the 0.5 ml well contains about 3x1010 mitochondria, as the well contains about 4 mg mitochondrial protein. Consequently, in the well the relation between number of fenozan molecules and number of mitochondria is about 100 (3x1012 / 3x1010 =100). One can assume that this concentration of the drug is embedded in the membrane and interacts with the lipid hydroperoxides. At 10-11 M fenozan concentration, the sample contains 3x109 fenozan molecule, and thus, the above calculated ration decreases to 0,1 fenozan molecule per one mitochondria. Probably, at such low concentration potassium fenozan form associates with water molecules and interacts with receptors on the surface of mitochondria (Ryzhkina IS et al, 2009). And, finally, at a concentration 10-22M, in the sample are almost no molecules potassium fenozan. In this case, the biological effect of the drug, apparently related to changes in the structure of water (M. Chaplin, 2000). These data suggest that the most effective use of the drug for medical purposes may be in the concentration range 10-9-10-14M, when the drug interacts with receptors of biological membranes. Future research should elucidate the mechanism of fenazan and similar biological active substances functioning at such extremely low concentration.
- Добавил в систему: Мохова Елена Николаевна