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Abstracts

XXIV conference

Drug Anphen as an adaptogen with broad spectrum of action

Zhigacheva I.V., Erokhin V.N., Volodkin A.A.

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, street Kosygin, 4, Moscow, 119334 Russia ; e-mail:zhigacheva@mail.ru

1 pp. (accepted)

Drugs - adaptogens improve the body's resistance to stress factors, by reducing the excessive generation of ROS by mitochondria (the main sources of ROS in these conditions). At the role of adaptogens in the first place pretend to the antioxidants, particularly synthetic phenolic antioxidants having relatively high coefficients interaction with the peroxyl radicals (k7). As the object of research was selected the drug anphen, which is a sterically hindered phenol-2- (carboxy) -2- (N-methylamido) -3- (3, 5-di-tert-butyl-4-hydroxyphenyl) propionate sodium.

Study of the effect of this drug on the generation of ROS and therefore on the activation of lipid peroxidation (LPO) was carried out on the model of the "aging" of rat liver mitochondria. Aging" caused the increase of ROS generation by mitochondria and the increase of the fluorescence intensity of the final products LPO 2.5 times. The drug in concentrations of 10-6M and 10-13M reduced the fluorescence intensity of LPO products in mitochondrial membranes almost to control values that may indicated the presence of antistress properties in the drug, which were investigated in animals subjected to stress. In the capacity of stress used a model of acute alcohol poisoning, which 1.4 times increase of the fluorescence intensity of LPO products in mitochondrial membranes of the liver. Introduction animal 10-6 M and 10-13 M anphen in 45 minutes before Introduction alcohol had reduced the fluorescence of LPO products to control values.

The injection of 10-13M of the drug to animals have led to changes in the characteristics of respiration and energy coupling liver mitochondria. Already after 30 min. of drug injection, the rates of oxidation of NAD-dependent substrates in the presence of ADP were increased by 13%, and after 1.5 hours – 16%. The respiratory control rates increased from 2.30 ± 0.10 to 2.83 ± 0.02. The rates of oxidation of succinate is not changed, but the efficiency of oxidative phosphorylation increased by 40%. In concentrations of 10-6 M and 10-13M anphen increased the survival rate of animals under conditions of hypoxia and acute alcohol poisoning. The lifespan of animals under various types of hypoxia were increased 1.8-4.5 times and 3.9 times - in the context of acute alcohol poisoning, and the survival of animals increased by 12-40%.

Moreover, at a concentration of 2.5×10-4M, the drug showed the radio protective properties, increasing the survival rate by 40% after irradiation with a dose of 650 R. Anphen showed antitumor properties: in concentrations of 2.8×10-4 and 2.8×10-5M it at 97-98% hindered the development of sarcoma 37 after transplantation of this tumor when administered to animals daily for 11 days.



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