Federal Science Institution: Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, Russia; Tel.: 8-495-939-74-09, e-mail: firstname.lastname@example.org
A disturbance of the antioxidant-prooxidant balance towards an increase in the production of reactive oxygen species (ROS) by mitochondria is a result of exposure to stress factors and it leads to development of a series of pathological states. We supposed that preparations having an antioxidant activity may prevent mitochondria from dysfunction under stress. It is well-known that sterically hindered phenols in most cases exhibit antioxidant properties. Therefore, we have chosen for studies the preparations that are sterically hindered phenols: anphen (1-acetylamido)-1-(3,5-di-tert-butyl-4-hydroxybenzyl)- sodium methylmalonate) and potassium phenozan (potassium salt of 2,6-di-tert-butyl-4-hydroxyphenyl-propionic acid). For solution of the problem, it was necessary to work out a model simulating a stress, i.e., to provide conditions for increasing the production of ROS by mitochondria and, consequently, for activating the lipid peroxidation (LPO). We solved the problem by creating a model of “aging” (incubation of mitochondria in a saline medium at room temperature). The incubation of mitochondria in a saline medium resulted in a twofold increase in the intensity of fluorescence of LPO products in mitochondrial membranes. Introduction of 10-6 and 10-13 M anphen or 10-8 - 10-16 M potassium phenozan into the mitochondria incubation medium resulted in a decrease in the LPO intensity to the control values. We studied the protective properties of the preparations using as a stress effect a model of acute alcoholic intoxication, acute hypobaric hypoxia (AHH), and low-temperature stress. These impacts resulted in activation of lipid peroxidation (LPO) and dysfunction of the rat liver mitochondria. The preparations under study used in concentrations of 10-12 to 10-18 M restored the bioenergetic functions of the rat liver mitochondria and decreased the LPO intensity to the control values. Moreover, the preparations at these concentrations increased 3.5 to 4.5 times the life span of the mice and increased the survival of the mice by 20 to 30% under conditions of different types of hypoxia, low-temperature stress, and acute alcoholic intoxication. Thus, the studies performed confirmed our hypothesis that preparations having antioxidant properties are adaptogens.