The Significance of Corticosteroid Binding to Plasma Proteins in the Mechanism of the Effect of the Radioprotector RS-11 on the Function of the Adrenal Cortex in Acute Radiation Sickness

Purpose: To study the role of binding of corticosteroids to blood plasma proteins in the mechanism of influence of the radioprotector RS-11 on the function of the adrenal cortex in irradiated animals.

Material and methods: The experiments were carried out on 30 male chinchilla rabbits weighing 2.5–3.0 kg. The first series of experiments is aimed at studying the reaction of the adrenal cortex and the processes of protein-steroid interaction after the administration of PC-11 to intact animals; in the second series – the same indicators in animals irradiated during the prophylactic administration of RS-11. The total content of 11-hydroxycorticosteroids (11-OKS) in blood plasma was determined by the fluorometric method of Guillemin et al in the author’s modification. The amount of free corticosteroids was determined by the difference in their content in whole plasma and in its protein fraction after separation on Sephadex G-25. Binding capacity of corticosteroid binding globulin (CSBG) was determined by gel filtration De Moor at al. in the author’s modification. Statistical analysis of the study results was carried out using the Student–Fisher method.

Results: In the group of intact rabbits under conditions of administration of PC-11, the reaction of the adrenal cortex after 2.5–3 hours was significantly higher compared to control animals. The increase in the free fraction of the hormone with the introduction of the radioprotector RS-11 during this period is associated with an increase in the total level of 11-OKS, since the binding ability of CSBG did not change. In the group of irradiated rabbits, 2.5–3 hours after irradiation, the administration of PC-11 also led to a significant increase in the total content of 11-OKS in the blood compared to the initial data. At the height of radiation sickness on the 4th day, RS-11 protected rabbits showed a significantly smaller decrease in the binding capacity of CSBG than control animals, and the total content of 11-OKS was higher than in the control. The level of free hormone on the 4th day was sharply reduced (8 % of the total 11-OKS content versus 41 % in the control). On the 8th day of radiation sickness, free 11-OKS in protected RS-11 and control rabbits was practically absent, however, in protected animals, the binding capacity of CSBG was 2 times higher than in control animals.

Conclusions: The influence of the radioprotector RS-11 leads in the first hours to an increase in the total concentration of 11-OX in the blood plasma and to an increase in the amount of free hormone in intact animals. The binding capacity does not change. Prophylactic administration of RS-11 inhibits, at the height of radiation sickness, the decrease in the binding capacity of CSBG in the blood plasma, and as a result, the increase in the level of free physiologically active hormone at a higher overall level of hormones in the blood. In the mechanism for reducing post-radiation hypercortisolism under conditions of protection with the drug RS-11, the main significance is the lesser degree of disruption of the binding ability of CSBG, and not a change in the overall level of hormones in the blood.