On the problem of impaired binding of corticosteroids to blood plasma proteins in the pathogenesis of acute radiation sickness

«Radiation and Risk», 2022, vol. 31, No. 3, pp.131-138

DOI: 10.21870/0131-3878-2022-31-3-131-138

Authors

Omelchuk N.N. – Head Dep., D. Sc., Biol., Prof. PFUR. Contacts: 6 Miklukho-Maclay str., Moscow, Russia, 117198. Tel.: +7 916-908-11-10; e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. .
Peoples' Friendship University of Russia, Moscow

Abstract

The study of violations of the binding of corticosteroids to blood plasma proteins in acute radiation syndrome allows us to clarify the mechanisms and patterns of pathological changes in the hormonal level of the body in the pathogenesis of acute radiation sickness. The relevance of the study is determined by the current risks of new man-made disasters and the threat to radiation safety. The results of the study make it possible to expand a number of theoretical positions of radiobiology on the main regularities of the binding of corticosteroids to blood plasma proteins, taking into account its various fractions, which make it possible to determine the role of free corticoids in the hormonal effect in acute radiation sickness. The purpose of this work is to study the main patterns of binding of corticosteroids to blood plasma proteins in the pathogenesis of acute radiation sickness in animals. The experiments were carried out on 20 male rabbits and 475 outbred rats. Previously experimental ani-mals were adapted to the conditions of the experiment. The total gama-irradiation of animals was carried out on the EGO-2 unit at an average dose rate of 575 R/min. Rabbits were irradiated at a dose of 8 Gy, rats at a dose of 8,5 Gy. The total content of 11-OCS was determined by the fluorimetric method 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. Results have been obtained demonstrating changes in the fractional composition of 11-OCS in blood plasma in the pathogenesis of acute radiation sickness in animals with mono- and biphasic curves of adrenocortical response to irradiation. Disturbances in the binding of corticosteroids to blood plasma proteins were found, resulting in an increase in free, biologically active hormones in the midst of radiation sickness. The presence in the blood plasma of non-protein-bound and therefore more mobile steroids can cause a hypercorticoid state with normal or even reduced levels of hormones in the blood. The long-term effect of "hidden" hypercortisolism, therefore, may be a factor that aggravates the clinical course of acute radiation sickness.

Key words
ionizing radiation, acute radiation sickness, adrenal cortex, adrenocortical reaction, corticosteroids, blood plasma, protein-steroid interaction, hypercorticism, 11-OCS-related, free hormone.

References

1. Anokhin P.K. Essays on the physiology of functional systems. Moscow, Book on Demand, 2021. 450 p. (In Russian).

2. Kuzin A.M. Structural-metabolic theory in radiobiology. Moscow, Nauka, 1986. 282 p. (In Russian).

3. Kudritsky Yu.K., Georgievsky A.B. Adaptation hypothesis of the biological effectiveness of ionizing radiation. Atomnaya energiya – Nuclear Power, 1992, vol. 13, no. 1, pp. 27-32. (In Russian).

4. Meyerson F.Z. Physiology of adaptation processes. Moscow, Nauka, 1986. 638 p. (In Russian).

5. Grebenyuk A.N., Strelova O.Yu., Legeza V.I., Stepanova E.N. Fundamentals of radiobiology and radiation medicine. Textbook. St. Petersburg, LLC FOLIANT Publishing House, 2012. 232 p. (In Russian).

6. Dokshina G.A. Endocrine and metabolic aspects of radiation sickness. Tomsk, Tomsk University Publishing House, 1984. 223 p. (In Russian).

7. Moroz B.B., Kendysh I.N. Radiobiological effect and endocrine factors. Moscow, Atomizdat, 1975. 228 p. (In Russian).

8. Fernandez-Real J.M., Pugeat M., Grasa M., Broch M., Vendrell J., Brun J., Ricart W. Serum corticosteroid-binding globulin concentration and insulin resistance syndrome: a population study. J. Clin. Endocrinol. Metab., 2002, vol. 87, no. 10, pp. 4686-4690.

9. Gagliardi L., Ho J.T., Torpy D.J. Corticosteroid-binding globulin: the clinical significance of altered levels and heritable mutations. Mol. Cell Endocrinol., 2010, vol. 316, no. 1, pp. 24-34.

10. Klieber M.A., Underhill C., Hammond G.L., Muller Y.A. Corticosteroid-binding globulin, a structural basis for steroid transport and proteinase-triggered release. J. Biol. Chem., 2007, vol. 282, no. 40, pp. 29594-29603.

11. Lewis J.G., Borowski K.K., Shand B.I., George P.M., Scott R.S. Plasma sex hormone-binding globulin, corticosteroid-binding globulin, cortisol, and free cortisol levels in outpatients attending a lipid disorders clinic: a cross-sectional study of 1137 subjects. Horm. Metab. Res., 2010, vol. 42, no. 4, pp. 274-279.

12. Lewis J.G., Elder P.A. Corticosteroid-binding globulin reactive center loop antibodies recognize only the intact natured protein: elastase cleaved and uncleaved CBG may coexist in circulation. J. Steroid. Biochem. Mol. Biol., 2011, vol. 127, no. 3-5, pp. 289-294.

13. Mihrshahi R., Lewis J.G., Ali S.O. Hormonal effects on the secretion and glycoform profile of corticosteroid-binding globulin. J. Steroid. Biochem. Mol. Biol., 2006, vol. 101, no. 4-5, pp. 275-285.

14. Sivukhina E.V., Jirikowski G.F., Bernstein H.G., Lewis J.G., Herbert Z. Expression of corticosteroid-bind-ing protein in the human hypothalamus, colocalization with oxytocin and vasopressin. Horm. Metab. Res., 2006, vol. 38, no. 4, pp. 253-259.

15. Zhou A., Wei Z., Stanley P.L., Read P.J., Stein P.E., Carrell R.W. The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release. J. Mol. Biol., 2008, vol. 380, no. 1, pp. 244-251.

16. Omelchuk N.N. Actual issues of prevention of acute radiation sickness. Natsionalnoye zdorovye – National Health, 2018, no. 1, pp. 70-75. (In Russian).

17. Omelchuk N.N. A method for assessing the functional activity of the adrenal cortex, taking into account the physiological role of different fractions of corticosteroids in the blood of healthy and irradiated animals. Natsionalnoye zdorovye – National Health, 2018, no. 1, pp 58-64. (In Russian).

18. Omelchuk N.N. Influence of thyroxine on the total level of corticosteroids and the binding capacity of cortico-steroid-binding globulin in blood plasma after irradiation. Natsionalnoye zdorovye – National Health, 2018, no. 1, pp. 65-69. (In Russian).

19. Pozdeev A.V. Experimental study of the content of cortisol in the blood during radiation exposure. Vestnik Kurskoy gosudarstvennoy selskokhozyaystvennoy akademii – Bulletin of the Kursk State Agricultural Academy, 2013, no. 7, pp. 53-54. (In Russian).

20. Guillemin R., Clayton G.W., Lipscomb H.S., Smith J.D. Fluorometric of rat plasma and adrenal, corticosterone concentration; a note on technical details. J. Lab. Clin. Med., 1959, vol. 53, no. 3. pp. 830-832.

21. De Moor P., Hoirwegh K., Heromans G., Declerck-Raskin M.M. Protein binding of corticosteroid studied by gel filtration. J. Clin. Invest., 1962, vol. 41, no. 4, pp. 816-827.

Full-text article (in Russian)