Роль связывания кортикостероидов с белками плазмы крови у облучённых животных в реализации эффектов радиопротекторов

Abstract

The article presents a comparative analysis of radioprotectors RS-10 and RS-11 ability to enhance radioresistance in animals exposed to radiation that is based on results of research on protein-steroid interaction in acute radiation sickness. The importance of the research is caused by the need to conduct a comprehensive analysis of the mechanisms of radioprotective action of synthetic radioprotectors, including the revealing of the role of corticosteroid binding to blood plasma proteins in irradiated animals. The aim of the research was to investigate the impact of RS-10 and RS-11 radioprotectors on the binding of corticosteroids to blood plasma proteins in irradiated animals. 90 male Chinchilla rabbits weighing 2.5-3.0 kg were included in the experimental research. At the initial stage of the research the response of the adrenal cortex and the processes of their binding to blood plasma proteins after administration of RS-10 and RS-11 to intact animals was studied; at the next stage the same rates were used for the follow-up of the animals exposed to radiation after prophylactic administration of the radioprotectors. The rabbits were totally irradiated with gamma rays at a dose of 8 Gy that caused acute radiation sickness of the IV degree. The RS-10 (chitosan bitartrate) at the dose of 10.0 mg/kg and the RS-11 (similar to RS-10, but with a lower average molecular mass) at the dose of 2-7 mg/kg were intravenously injected to rabbits 15 minutes before the irradiation. Control animals were injected with an equal volume of the saline. The total content of 11-oxycorticosteroids (11-OCS) in the blood plasma was quantitated with the use of the fluorometric method in the author's modification. The amount of free corticosteroids was quantified as the difference between their content in the whole plasma and in its protein fraction after the gel-filtration chromatography with Sephadex G-25. The binding capacity of corticosteroid-binding globulin (CBG) was determined by gel filtration in the author's modification. The results of the study demonstrated the rise of the concentration of the blood plasma corticosteroids in the first hours after the RS-10 and RS-11 injection to intact animals, the amount of the free hormone increased as well. The effect of RS-10 on the rise of the free hormone levels was more pronounced as compared to the RS-11 effect. The impact of both radioprotectors on the elevation of the amount of 11-OCS binding to blood plasma proteins was similar. The introduction of RS-10 and RS-11 to the animals did not have effect on the binding capacity of the blood plasma proteins. The mechanism of radioprotective action of RS-10 and RS-11 in irradiated animals is the establishment of the optimal response of the adrenal cortex in the first hours after irradiation. The difference of the early adrenocortical response in animals irradiated and protected due to the injection of RS-10 and RS-11 from the optimal response varying towards strengthening or weakening, is the indicator of the radiation sickness severity. Prophylactic administration of RS-10 and RS-11 to irradiated animals at the height of the disease inhibited the reduction of the binding capacity of the CBG, resulting in the rise of the free hormone level at the higher total level of hormones in the blood is inhibited as well. In the mechanism for reducing post-radiation hypercorticism, with the use of the radioprotectors of RS-10 and RS-11, the main importance is the lower degree of the CBG binding capacity impairment rather than the change in the overall level of blood hormones. The higher prophylactic effect of RS-11 compared to RS-10 is confirmed by the significantly high rate of the binding ability of the CBG at the height of radiation sickness and the lower mortality among the animals involved in the experimental research.