Peculiarities of the blood oxygen and antioxidant status in the children presenting with somatotrophic insufficiency and managed by the substitution treatment with growth hormone

The present work was designed to study the influence of therapy with recombinant growth hormone on the oxygen and antioxidant blood status in the children presenting with somatotrophic insufficiency. A total of 11 children (2 girls and 9 boys) at the age from 3 to 9 years with confirmed somatotrophic insufficiency were available for the observation. They had never before been treated with growth hormone preparations. The blood oxyhemoglobin level and superoxide dismutase (SOD) activity increased within 3 months after the onset of therapy. There is direct correlation between oxyhemoglobin levels and SDS for the growth rate (r= 0.64; p<0.05) and negative correlation between mean hemoglobin content in erythrocytes (MHCE) and SDS for the growth rate (r=-0.69), p<0.05). The results of the study suggest the close relationship between the system of growth hormone/growth factors and the morphofunctional state of erythrocytes. It is concluded that the short-term treatment of the children suffering somatotrophic insufficiency with recombinant growth hormone appears to promote the development of adaptive mechanisms.

somatotrophic insufficiency, recombinant growth hormone, erythrocytes, hemoglobin, efficacy of oxygen transport, antioxidant status

1. Rosén T., Bengtsson B.A. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 1990; 336: 8710: 285-288.

2. Johansson J.O., Fowelin J., Landin K., Lager I., Bengtsson B.A. Growth hormone-deficient adults are insulin-resistant. Metabolism 1995; 44: 9: 1126-1129.

3. Russell-Jones D.L., Watts G.F., Weissberger A., Naoumova R., Myers J., Thompson G.R., Sönksen P.H. The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients. Clin Endocrinol (Oxford) 1994; 41: 3: 345-350.

4. Kerr M.E., Bender C.M., Monti E.J. An introduction to oxygen free radicals. Heart Lung 1996; 25: 3: 200-209; 210-211.

5. Ungvari Z., Sosnowska D., Podlutsky A., Koncz P., Sonntag W.E., Csiszar A. Free radical production, antioxidant capacity, and oxidative stress response signatures in fibroblasts from Lewis dwarf rats: effects of life span-extending peripubertal GH treatment. J Gerontol A Biol Sci Med Sci 2011; 66: 5: 501-510.

6. Evans L.M., Davies J.S., Anderson R.A., Ellis G.R., Jackson S.K., Lewis M.J., Frenneaux M.P., Rees A., Scanlon M.F. The effect of GH replacement therapy on endothelial function and oxidative stress in adult growth hormone deficiency. Eur J Endocrinol 2000; 142: 3: 254-262.

7. Ferrari R., Guardigli G., Mele D., Percoco G.F., Ceconi C., Curello S. Oxidative stress during myocardial ischaemia and heart failure. Curr Pharm Des 2004; 10: 14: 1699-1711.

8. Brun J.F. Hormones, metabolism and body composition as major determinants of blood rheology: potential pathophysiological meaning. Clin Hemorheol Microcirc 2002; 26: 2: 63-79.

9. Sohmiya M., Kato Y. Effect of long-term administration of recombinant human growth hormone (rhGH) on plasma erythropoietin (EPO) and haemoglobin levels in anaemic patients with adult GH deficiency. Clin Endocrinol (Oxford) 2001; 55: 6: 749-754.

10. Christ E.R., Cummings M.H., Westwood N.B., Sawyer B.M., Pearson T.C., Sönksen P.H., Russell-Jones D.L. The importance of growth hormone in the regulation of erythropoiesis, red cell mass, and plasma volume in adults with growth hormone deficiency. J Clin Endocrinol Metab 1997; 82: 9: 2985-2990.

11. Ramos S.B., Brun J.F., Gray B., Rogerson S., Weatherby R.P., Tajouri L., Marshall-Gradisnik S.M. The effects of short term recombinant human growth hormone (rhGH) on blood rheology in healthy young males. Clin Hemorheol Microcirc 2011; 47: 2: 121-129.

12. Brazhe N.A., Baizhumanov A.A., Parshina E.I., Iusipovich A.I., Akhalaia M.I., Iarlykova I., Labetskaia O.I., Ivanova S.M., Morukov B.V., Maksimov G.V. Studies of the blood antioxidant system and oxygen-transporting properties of human erythrocytes during 105-day isolation. Aviakosm Ekolog Med 2011; 45: 40-45.

13. Akhalaia M.I., Baizhumanov A.A., Brazhe N.A., Luneva O.G., Mikhailov I.V., Bryzgalova N.Y., Parshina E.Y., Maksimov G.V., Rubin A.B. Modifying effect of nitric oxide on rat blood plasma proteins and hemoglobin. Dokl Biochem Biophys 2007; 415: 222-224.

14. Yusipovich A.I., Parshina E.Y., Brysgalova N.Y., Brazhe A.R., Brazhe N.A., Lomakin A.G., Levin G.G., Maksimov G.V. Laser interference microscopy in erythrocyte study. J Appl Phys 2009; 105: 102037-1-102037-7.

15. Соловьев К.Н., Гладков Л.Л., Старухин А.С., Шкирман С.Ф. Спектроскопия порфиринов: Колебательные состояния. Наука и техника (Минск) 1985.

16. Юсипович А.И., Брызгалова Н.Ю., Паршина Е.Ю., Ломакин А.Г., Родненков О.В., Левин Г.Г., Максимов Г.В., Рубин А.Б. Применение лазерной интерференционной микроскопии для оценки формы и состояния эритроцитов. Бюлл эксп биол 2008; 3: 357-360.

17. Schindelin J., Arganda-Carreras I., Frise E., Kaynig V., Longair M., Pietzsch T., Preibisch S., Rueden C., Saalfeld S., Schmid B., Tinevez J.Y., White D.J., Hartenstein V., Eliceiri K., Tomancak P., Cardona A. Fiji: an open-source platform for biological-image analysis. Nat Meth 2012; 9: 676-682.

18. Gedde M.M., Yang E., Huestis W.H. Shape response of human erythrocytes to altered cell pH. Blood 1995; 86: 1595-1599.

19. Kosaka H., Seiyama A. A physiological role of nitric oxide as an enhancer of oxygen transfer from erythrocytes to tissues. Biochem Biophys Res Commun 1996; 218: 749-752.

20. Hobbs A.J., Gladwin M.T., Patel R.P., Williams D.L., Butler A.R. Haemoglobin: NO transporter, NO inactivator or Nоne of the above? Trends Pharmacol Sci 2002; 23: 406-411.

21. Stamler J.S., Simon D.I., Osborne J.A., Mullins M.E., Jaraki O., Michel T., Singel D.J., Loscalzo J. S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds. Proceedings of the National Academy. Sciences 1992; 89: 444-448.