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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2016; 62(4): 31-39


S.I. Uretii1, A.V. Kotsuruba2, B.S. Kopyak2

  1. O.O.Bogomolets national medical university, Ministry of Health of Ukraine, Kyiv;
  2. O.O.Bogomolets Institute of Physiology, National Academy of Scienes of Ukraine, Kyiv


In experiments in vivo we studied the effect of chronic ironcontained drug (Urfuhem) supplemention on the level of hemoglobin (Hb) in the blood of aging rats. To establish the biochemical mechanisms of drug action it were determined the parameters of oxidative/nitrosative stress and the hydrogen sulfide level in plasma and erythrocytes, the level of non-heme iron in plasma and erythrocytes sensitivity to acid hemolysis. It was found that in aging rats the drug significantly increases the Hb content of red blood cells and reduces its resistance to acid hemolysis. After the drug supplemention the rate of superoxide anion-radical (*O2 - ) generation in erythrocytes and stable hydrogen peroxide (H2O2) content both in plasma and erythrocytes were down-regulated. The drug did not reduce the high levels of generation of the hydroxyl radical (*OH) and high levels of excess NO de novo synthesis by iNOS in erythrocytes but reduced the pools of nitrate anion (NO3 - ) and its reutilization for NO synthesis. After the drug supplemention the rate of constitutine NO synthesis by cNOS in aging rats plasma was up-regulated perhaps by cNOS coupling. The results indicate that the reason for increasing the permeability of the proton (H+) in red blood cells that causes the acid hemolysis in aging rats after the drug supplemention can be change in the balance of levels of oxidative and nitrosative stress in red blood cells in favor of the latter, and that toxic *OH generation is not at the expense of the classical Fenton reaction in the presence of iron ions (Fe2+), but due to the formation and decomposition of peroxynitrite (ONOO-).

Keywords: hemoglobin; red blood cells; аcid hemolysis; oxidative and nitrosative stress; iron-соntained drug; old rats


  1. Kotsuruba AV, Sharipov RR,Kopyak BS, Sagach VF. Brain focal ischemia-reperfusion causes a decreased resistance of erythrocytes from venous blood to acid hemolysis, which is prevented by ecdysterone. Fiziol Zh. 2015; 61(5):3-10. [Ukrainian]. CrossRef  
  2. Kotsuruba AV, Kopjak BS, Sagach VF, Spivak NJ. Nanocerium restores the erythrocytes stability to acid hemolysis by inhibition of oxygen and nitrogen reactive species in old rats. Fiziol Zh. 2015; 61(1):3-9. CrossRef  
  3. Sikora J, Orlov SN, Furuya K, Grygorczyk R. Hemolysis is a primary ATP-release mechanism in human erythrocytes. Blood. 2014; 124(13):2150-7. CrossRef PubMed PubMedCentral
  5. Giebink AW, Vogel PA, Medawala W, Spence DM. Cpeptide-stimulated nitric oxide production in a cultured pulmonary artery endothelium is erythrocyte mediated and requires Zn(2+). Diabetes Metab Res Rev. 2013; 29(1):44-52. CrossRef PubMed
  7. Wu L, Wang R.Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol Rev. 2005; 57(4):585-630. CrossRef PubMed
  9. Westphal M, Weber TP, Meyer J, von Kegler S, Van Aken H, Booke M. Affinity of carbon monoxide to hemoglobin increases at low oxygen fractions. Biochem Biophys Res Commun. 2002; 295(4):975-7. CrossRef  
  10. Sahach VF, Doloman LB, Kotsiuruba AV, Bukhanevich OM, Kurdanov KhA, Beslanieiev IA, Bekuzarova SA. Increased level of nitric oxide stable metabolites in the blood of highlanders. Fiziol Zh. 2002; 48(5):3-8. [Ukrainian]. CrossRef  
  11. Valentine WN, Toohey JI, Paglia DE, Nakatani M, Brockway RA.Modification of erythrocyte enzyme activities by persulfides and methanethiol: possible regulatory role. Proc Natl Acad Sci U S A. 1987; 84(5):1394-8. CrossRef PubMed PubMedCentral
  13. Cortese-Krott MM, Kelm M.Endothelial nitric oxide synthase in red blood cells: key to a new erythrocrine function? Redox Biol. 2014; 2:251-8. CrossRef PubMed PubMedCentral
  15. Vitvitsky V, Yadav PK, Kurthen A, Banerjee R.Sulfide oxidation by a noncanonical pathway in red blood cells generates thiosulfate and polysulfides. J Biol Chem. 2015; 290(13):8310-20. CrossRef PubMed PubMedCentral
  17. Matallo J, Vogt J, McCook O, Wachter U, Tillmans F, et al. Sulfide-inhibition of mitochondrial respiration at very low oxygen concentrations. Nitric Oxide. 2014; 41:79-84. CrossRef PubMed PubMedCentral
  19. Savolainen H. High Toxicity of Hydrogen Sulfide by the Inhibition of Mitochondrial Respiration. J Biol Chem. 2010; 285(24): le9. CrossRef PubMed PubMedCentral
  21. Cooper CE. Nitric oxide and iron proteins. Biochim Biophys Acta. 1999; 1411(2-3):290-309. CrossRef  
  22. Terskov IA, Gittelzon II. Method chimicheskich (kislotnich) erytrogram. Biophysika. 1957; 2(2):259-66. [Russian].
  24. Kotsuruba AV, Kopjak BS, Sagach VF, Spivak Nja. Old rats erythrocytes stability to acid hemolysis restoring by cerium oxide nanoparticles. Fiziol Zh. 2014; 60(6):3-9. [Ukrainian]. CrossRef  
  25. Drachuk K.O., Kotsiuruba A.V., Bazilyuk, Stepanenko L.G., Sagach V.F. Propagylglycine restores endotheliumdependent relaxetion of aortic smooth muscles in old rats. Fiziol Zh. 2014; 60(4):3-10. [Ukrainian]. CrossRef PubMed
  27. Scheuplein F, Schwarz N, Adriouch S, Krebs C, Bannas P,et al. NAD+ and ATP released from injured cells induce P2X7-dependent shedding of CD62L and externalization of phosphatidylserine by murine T cells. J Immunol. 2009; 182(5):2898-908. CrossRef PubMed
  29. Fan Q, Chen M, Fang X, Lau WB, Xue L,et al. Aging might augment reactive oxygen species (ROS) formation and affect reactive nitrogen species (RNS) level after myocardial ischemia/reperfusion in both humans and rats. Age (Dordr). 2013; 35(4):1017-26. CrossRef PubMed PubMedCentral
  31. Colombo G, Dalle-Donne I, Giustarini D, Gagliano N, Portinaro N, et al. Cellular redox potential and hemoglobin S-glutathionylation in human and rat erythrocytes: A comparative study. Blood Cells Mol Dis. 2010; 44(3):133-9. CrossRef PubMed
  33. Dafre AL, Reischl E. Hemoglobin S-thiolation during peroxide-induced oxidative stress in chicken blood. Comp Biochem Physiol C Toxicol Pharmacol. 2006; 142(3-4):188-97. CrossRef PubMed
  35. Sahach VF, Kotsiuruba AV, Baziliuk OV, Mehed' OF, Stepanenko LH. Inhibitors of arginase pathway in L-arginine metabolism as a new class of antihypertensive drugs: action of urea on oxidative and nonoxidative metabolism of L-arginine and vascular tone in chronic hypertension. Fiziol Zh. 2004; 50(6):9-18. [Ukrainian]. CrossRef PubMed
  37. Sagach VF, Bondarenko A, Bazilyuk OV, Kotsuruba AV. Endothelial dysfunction: possible mechanisms and ways of correction. Experimental & Clinical Cardiology. 2006; 11(2):107-112. [Ukrainian]. PubMed PubMedCentral
  39. Jennings ML. Transport of H2S and HS(-) across the human red blood cell membrane: rapid H2S diffusion and AE1-mediated Cl(-)/HS(-) exchange. Am J Physiol Cell Physiol. 2013; 305(9):C941-50. CrossRef PubMed PubMedCentral
  41. Goubern M, Andriamihaja M, Nübel T, Blachier F, Bouillaud F. Sulfide, the first inorganic substrate for human cells. FASEB J. 2007; 21(8):1699-1706. CrossRef PubMed
  43. Kimura H. Hydrogen sulfide and polysulfides as signaling molecules. Proc Jpn Acad Ser B Phys Biol Sci. 2015; 91(4):131-59. CrossRef PubMed PubMedCentral
  45. Kimura H. Hydrogen sulfide and polysulfides as biological mediators. Molecules. 2014; 19(10):16146-57. CrossRef PubMed
  47. Hristov KL, Gagov HS, Itzev D, Duridanova DB. Heme oxygenase-2 products activate IKCa: role of CO and iron in guinea pig portal vein smooth muscle cells. J Muscle Res Cell Motil. 2004; 25(4-5):411-21. CrossRef PubMed
  49. Ahmmed GU, Xu Y, Hong Dong P, Zhang Z, Eiserich J, Chiamvimonvat N. Nitric oxide modulates cardiac Na(+) channel via protein kinase A and protein kinase G. Circ Res. 2001; 89(11):1005-13. CrossRef PubMed
  51. Schmidt A, Kolb E, Hofmann U, Gründel G, Nestler K, Schmidt U.The content of Hb in blood and the protein, Fe, Fe-binding capacity, Cu and Zn in blood plasma of low parity sows before and after oral iron administration. Arch Exp Veterinarmed. 1990; 44(3):439-46. PubMed
  53. Ahiboh H, Oga AS, Yapi HF, Kouakou G, Boua KD, et al. Anaemia, iron index status and acute phase proteins in malaria (Abidjan, Côte d'Ivoire). Bull Soc Pathol Exot. 2008; 101(1):25-8. PubMed
  55. Clanton TL, Hogan MC, Gladden LB. Regulation of cellular gas exchange, oxygen sensing, and metabolic control. Compr Physiol. 2013; 3(3):1135-90. CrossRef

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