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Abstracts

XX conference

Model for assessment of biologiucal active compounds protective action

Zhigacheva I.V., Burlakova E.B., Goloschapov A.N.

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, Moscow, 119334 Russia

1 pp. (accepted)

Mitochondria, being one of the regulators of the energy metabolism, play an important role in the organism response to stress condition. Approximately 1-3% of mitochondrial oxygen consumption by 1 electron reduction forms a reactive oxygen species (ROS). In physiological conditions, antioxidant systems neutralize excessive ROS production, and supports their concentration at low picomolar level [Crack PJ, Taylor J.M., 2005].. Shift antioxidant - prooxidant ratio toward increasing production of ROS leads to oxidative stress. Shift this balance effects under the influence of various stressors. Quite urgent problem of finding new drugs with adaptogenic properties. According to the literature [Cherniak B. 2010] under stress mitochondria are the main source of ROS mitochondria. On this basis, it was possible to suggest that these agents should primarily affect the generation of ROS by these organelles. And this role is primarily claiming antioxidants.

Since it is known that sterically hindered phenols, in most cases, have antioxidant properties [Emanuel N.M, Lipchina L.P, 1958] as the object of study was selected product potassium penozan (potassium salt of 2,6-di-tret-butyl-4-hydroxyphenyl-propionic acid and anphen (sodium salt of 1-N-( acetylamido)-1-(3,5- di-tret-butyl-4-hydroxyphenyl)- metyl-malonat). Since the main source of stress ROS are the mitochondria, it was necessary to develop a model for simulating stress, ie find conditions under which it will increase production of ROS by mitochondria, and thus will be activated lipid peroxidation (LPO). To activation LPO has developed a model of “aging” – long-term incubation mitochondria in saline medium. Incubation of mitochondria in saline media leads to the activation of free radical oxidation, and hence the fluorescence intensity of lipid peroxidation products At the same time the content of lipid peroxidation products increased by 3-4 times. Administration of drugs to the incubation medium of mitochondria decreased the fluorescence of LPO, and this reduction was dependent of the concentration of drugs in the incubation medium. Potassium phenozan in 10-8 - 10-16M or anphen in10-6M, 10-13M concentration decreased the fluorescence intensity of lipid peroxidation products in the membranes of rat liver mitochondria to control values. Parenteral administration of drugs in these concentrations prevented changes in the bioenergetic characteristics of rat liver mitochondria in acute hypobaric hypoxia and in 3.5-4.5 fold increased Parenteral administration of drugs in these concentrations o prevented changes in the bioenergetic characteristics of rat liver mitochondria in acute hypobaric hypoxia and in 3.5-4.5 fold increased the duration of life and a 20-30% increase in survival of mice in different types of hypoxia and acute alcohol poisoning



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