Ukr.Biochem.J. 2014; Volume 86, Issue 3, May-Jun, pp. 114-124


Antioxidant status and glutathione redox potential of erythrocytes in patients with acute coronary syndrome

I. V. Buko1, L. Z. Polonetsky1, A. G. Mrochek1, A. G. Moiseenok2

1Republican Scientific-Practical Center Cardiology, Minsk;
2Scientific-Practical Center for Foodstuffs,
National Academy of Sciences of Belarus, Minsk

Indicators of oxidative stress (OS), systemic inflammation, metabolism and redox status of glutathione (GSH) were investigated and compared in patients with ST-segment elevation myocardial infarction on electrocardiograms (STEMI), and patients with unstable angina (UA). The elevated and decreased myeloperoxidase level, superoxide dismutase activity, and moderate increased plasma levels­ of interleukin-6, while maintaining the antioxi­dant potential, were found in Group 1. Disor­ders in pro-/antioxidant balance and systemic inflammatory response were manifested in UA. Increased GSH concentration (and total GSH) in erythrocytes has been established for STEMI patients and the decreased GSH for UA patients. Thus, a significant shift of erythrocytes redox to oxidization and increase (unlike STEMI patients) of glutathione peroxidase activity were recorded. Mechanisms of the pro- and antioxidant functions of red blood cells in acute coronary syndrome are considered. The role of red blood cell glutathione to provide more oxidized intravascular environment for S-glutathionylation and optimization of redox signa­ling in target cells is pronounced.

Keywords: , , , ,


  1. Jones DP. Radical-free biology of oxidative stress. Am. J. Physiol. Cell Physiol. 2008;295(4):C849–C868. PubMed, PubMedCentral
  2. Martinovich GG, Cherenkevich SN. The redox processes in cells. Mn.: BSU, 2008. 159 p.
  3. Hansen JM, Go YM, Jones DP. Nuclear and mitochondrial compartmentation of oxidative stress and redox signaling. Annu Rev Pharmacol Toxicol. 2006;46(1):215-34. Review. PubMed, CrossRef
  4. Go YM, Jones DP. Redox compartmentalization in eukaryotic cells. Biochim Biophys Acta. 2008 Nov;1780(11):1273-90. Review. PubMed, PubMedCentral, CrossRef
  5. Lushchak V.I. Glutathione homeostasis and functions: potential targets for medical interventions. J Amino Acids. 2012:2012:1-26. PubMed, PubMedCentral, CrossRef
  6. Jones DP. Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol. 2002;348:93-112. PubMed, CrossRef
  7. Harris C, Hansen JM. Oxidative stress, thiols, and redox profiles. Methods Mol Biol. 2012;889:325-46. PubMed, CrossRef
  8. Kulinsky VI, Kolesnichenko LS. Glutathione system. I. Synthesis, transport, glutathione transferases, glutathione peroxidases. Biomed Khim. 2009 May-Jun;55(3):255-277. PubMed
  9. Kulinsky VI, Kolesnichenko LS. Glutathione system. II. Other enzymes, thiol-disulphide metabolism, inflammation and immunity, functions. Biomed Khim. 2009 Jul-Aug;55(4):365–379. Russian. PubMed
  10. Ashfaq S, Abramson JL, Jones DP, Rhodes SD, Weintraub WS, Hooper WC, Vaccarino V, Alexander RW, Harrison DG, Quyyumi AA. Endothelial function and aminothiol biomarkers of oxidative stress in healthy adults. Hypertension. 2008 Jul;52(1):80-5. PubMed, PubMedCentral, CrossRef
  11. Moussa S. A. Oxidative stress in diabetes mellitus. Rom. J. Biophys. 2008;18(3):225–236.
  12. Morris CR, Suh JH, Hagar W, Larkin S, Bland DA, Steinberg MH, Vichinsky EP, Shigenaga M, Ames B, Kuypers FA, Klings ES. Erythrocyte glutamine depletion, altered redox environment, and pulmonary hypertension in sickle cell disease. Blood. 2008 Jan 1;111(1):402-10. Epub 2007 Sep 11. PubMed, PubMedCentral
  13. Jones DP, Liang Y. Measuring the poise of thiol/disulfide couples in vivo. Free Radic Biol Med. 2009 Nov 15;47(10):1329-38. PubMed, PubMedCentral, CrossRef
  14. Minetti M, Malorni W. Redox control of red blood cell biology: the red blood cell as a target and source of prooxidant species. Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1165-9. Review. PubMed, CrossRef
  15. Matteucci E, Giampietro O. Thiol signalling network with an eye to diabetes. Molecules. 2010 Dec 6;15(12):8890-903. Review. PubMed, CrossRef
  16. Go YM, Jones DP. Cysteine/cystine redox signaling in cardiovascular disease. Free Radic Biol Med. 2011 Feb 15;50(4):495-509.  PubMed, PubMedCentral, CrossRef
  17. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972 Jun;18(6):499-502. PubMed
  18. Gorudko IV, Cherkalina OS, Sokolov AV, Pulina MO, Zakharova ET, Vasil’ev VB, Cherenkevich SN, Panasenko OM. New approaches to the measurement of the concentration and peroxidase activity of myeloperoxidase in human blood plasma. Bioorg Khim. 2009 Sep-Oct;35(5):629-39.  Russian. PubMed
  19. Timoshenko AV, Cherenkevich SN, Gabius HJ. Viscum album agglutinin-induced aggregation of blood cells and the lectin effects on neutrophil function. Biomed Pharmacother. 1995;49(3):153-8. PubMed, CrossRef
  20. Korobeynikova EN. Modification of the determination of lipid peroxidation products in a reaction with thiobarbituric acid. Lab. Delo. 1989;(7):8-10. PubMed
  21. Ragino YuI, Dushkin MI. A simple method of studying oxidation resistance of heparin- precipitated blood serum beta-lipoproteins.  Klin Labor Diagnostika. 1998;(3):6-9.
  22. Chevari S., Andyal T., Shtrenger Ya. Determination of the antioxidant properties of the blood and their diagnostic significance in the elderly.  Lab Delo. 1991;(10):9-13. PubMed
  23. Gavrilova AR, Khmara NF. Determination of glutathione peroxidase activity in erythrocytes in saturated concentrations of the substrate. Lab Delo. 1986;(12):721-4. Russian. PubMed
  24. Beutler E. Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies. J Clin Invest. 1969 Oct;48(10):1957-66. PubMed, PubMedCentral, CrossRef
  25. Koroliuk MA, Ivanova LI, Mayorova IG, Tokarev VE.  A method of determining catalase activity. Lab Delo. 1988;(1):16-9. Russian. PubMed
  26. Promyslov MSh, Demchuk ML. A modified method of determination of the total serum antioxidant activity. Vopr Med Khim. 1990 Jul-Aug;36(4):90-2. PubMed
  27. Akerboom TP, Sies H. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol. 1981;77:373-82. PubMed, CrossRef
  28. Schafer FQ, Buettner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001 Jun 1;30(11):1191-212. Review. PubMed, CrossRef
  29. Halafyan A. A. STATISTICA 7. Statistics Data Analysis. Moscaw. “Binom-Press”, 2007. 512 p.
  30. Menshchikova E. B., Zenkov N. K., Lankin V. Z. et al. Oxidative stress. Pathological states and diseases. Novosibirsk: ARTA, 2008. 284 p.
  31. Monaco C, Mathur A, Martin JF. What causes acute coronary syndromes? Applying Koch’s postulates. Atherosclerosis. 2005 Mar;179(1):1-15. Review. PubMed, CrossRef
  32.  García-Pinilla JM, Gálvez J, Cabrera-Bueno F, Jiménez-Navarro M, Gómez-Doblas JJ, Galisteo M, Camuesco D, de Teresa Galván C, Espinosa-Caliani S, Zarzuelo A, de Teresa-Galván E. Baseline glutathione peroxidase activity affects prognosis after acute coronary syndromes. Tex Heart Inst J. 2008;35(3):262-7. PubMed, PubMedCentral
  33. Iqbal MP, Ishaq M, Mehboobali N. Increased levels of erythrocyte glutathione in acute myocardial infarction: an antioxidant defence. J Pak Med Assoc. 2004 May;54(5):254-258.  PubMed
  34. Shinde S, Kumar P, Patil N. Decreased levels of erythrocyte glutathione in patients with myocardial infarction. Internet J Altern. Med. 2005; 2:1. CrossRef
  35. Usal A, Acartürk E, Yüregir GT, Unlükurt I, Demirci C, Kurt HI, Birand A. Decreased glutathione levels in acute myocardial infarction. Jpn Heart J. 1996 Mar;37(2):177-82. PubMed, CrossRef
  36. Kharb S. Low blood glutathione levels in acute myocardial infarction. Indian J Med Sci. 2003 Aug;57(8):335-7. PubMed
  37. Palanisamy P, Yagneswara  RY, Jawahar F,  Ganesan  S. Oxidative  Stress  and Cardiac Biomarkers in Patients with Acute Myocardial Infarction. Eur J Sci Res. 2009;27(2):275-285.
  38. De Chiara B, Mafrici A, Campolo J, Famoso G, Sedda V, Parolini M, Cighetti G, Lualdi A, Fiorentini C, Parodi O. Low plasma glutathione levels after reperfused acute myocardial infarction are associated with late cardiac events. Coron Artery Dis. 2007 Mar;18(2):77-82. PubMed, CrossRef
  39. Pietruszyński R, Markuszewski L, Masiarek K, Makowski M, Retelewska W, Watala C. Role of preprocedural glutathione concentrations in the prediction of major adverse cardiac events in patients with acute coronary syndrome treated with percutaneous coronary intervention. Pol Arch Med Wewn. 2013;123(5):228-37. PubMed
  40. Sapira V, Craiu E, Adumitresi C. Glutathione peroxidase activity affects prognosis in non-st segment elevation acute coronary sindrom. Fiziologia-Physiology. 2009;19(3):16 p.
  41. Blankenberg S, Rupprecht HJ, Bickel C, Torzewski M, Hafner G, Tiret L, Smieja M, Cambien F, Meyer J, Lackner KJ; AtheroGene Investigators. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease. N Engl J Med. 2003 Oct 23;349(17):1605-13. PubMed
  42. Delmastro M. M., Piganelli J. D. Oxidative Stress and Redox Modulation Potential in Type 1 Diabetes. Clin Dev Immunol. 2011;2001:1-15. PubMedPubMedCentral, CrossRef
  43. Gunaldi M, Helvaci A, Zorlu M, Kiskac M, Ekmen N, Yilmaz G. Alteration in serum levels of selenium and glutathione peroxidase in acute myocardial infarction. Oxid. Antioxid Med. Sci. 2012;1(3):175–178. CrossRef
  44. Pyrochkin A.V., Moyseenok A.G. The effectiveness of the combined application of functionally related vitamins and selenium for the correction of endothelial dysfunction and the elasticity of the arteries in patients with coronary heart disease and myocardial infarction. Meditsinskie Novosti. 2009;182(14):77-81.
  45. Forgione MA, Cap A, Liao R, Moldovan NI, Eberhardt RT, Lim CC, Jones J, Goldschmidt-Clermont PJ, Loscalzo J. Heterozygous cellular glutathione peroxidase deficiency in the mouse: abnormalities in vascular and cardiac function and structure. Circulation. 2002 Aug 27;106(9):1154-8. PubMed, CrossRef
  46. Tsantes AE, Bonovas S, Travlou A, Sitaras NM. Redox imbalance, macrocytosis, and RBC homeostasis. Antioxid Redox Signal. 2006 Jul-Aug;8(7-8):1205-16. Review. PubMed, CrossRef
  47. Noh JY, Lim KM, Bae ON, Chung SM, Lee SW, Joo KM, Lee SD, Chung JH. Procoagulant and prothrombotic activation of human erythrocytes by phosphatidic acid. Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H347-55. PubMed, CrossRef
  48. Pastore A, Piemonte F. S-Glutathionylation signaling in cell biology: progress and prospects. Eur J Pharm Sci. 2012 Aug 15;46(5):279-92. Review. PubMed, CrossRef
  49. Xiong Y, Uys JD, Tew KD, Townsend DM. S-glutathionylation: from molecular mechanisms to health outcomes. Antioxid Redox Signal. 2011 Jul 1;15(1):233-70. Review. PubMed, PubMedCentral, CrossRef
  50. Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, Freeman BA. Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science. 2002 Jun 28;296(5577):2391-4. PubMed, CrossRef
  51. Petina G. V. Effect of thiol-disulfide system, oxidative modification of proteins on the neutrophil function under oxidative stress. Avt. diss. … kand. med. nauk.  2009. 24 p.
  52. Elewa H., Zalat ZA, Oriquat G, Rifaat R, El-Hadidy W, Yacoub S. Low-dose captopril and antioxidant combination as adjunct therapy in type-2 diabetic patients with coronary artery disease: A preliminary study.  J. Diabetology. 2011 October;3(4):1-10.

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.