Advertisement

Protective efficacy of dinitrosyl iron complexes with reduced glutathione in cardioplegia and reperfusion

  • Oleg PisarenkoEmail author
  • Irina Studneva
  • Alexander Timoshin
  • Oksana Veselova
Molecular and cellular mechanisms of disease
  • 59 Downloads
Part of the following topical collections:
  1. Molecular and cellular mechanisms of disease

Abstract

Disturbed homeostasis of nitric oxide (NO) is one of the causes of myocardial ischemia/reperfusion (I/R) injury during open-heart surgery. This study was designed to explore mechanisms of action of dinitrosyl iron complexes with reduced glutathione ({(GS)2Fe+(NO+)2}+, DNIC-GS) added to crystalloid cardioplegia or reperfusion solution in isolated working rat hearts. Hearts of male Wistar rats were subjected to cardioplegic arrest by St. Thomas’ Hospital cardioplegic solution (STH) and normothermic global ischemia followed by reperfusion. DNIC-GS were used with STH or during early reperfusion. Lactate dehydrogenase (LDH) activity in the coronary effluent and myocardial contents of adenine nucleotides, phosphocreatine, and lactate were determined spectrophotometrically. Reactive oxygen species (ROS) formation in the coronary effluent and myocardial DNIC content was assessed by EPR technique. Cardioplegia or reperfusion with DNIC-GS significantly improved recovery of coronary flow and cardiac function compared with control. Carboxy-[2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidozoline-1-oxy-3-oxide] (C-PTIO), a selective NO scavenger, reduced/abolished protective action of DNIC-GS. Enhanced recovery of cardiac function with DNIC-GS reduced LDH release in the coronary effluent, augmented recovery of myocardial energy state, and decreased formation of ROS-generating systems at reperfusion. Beneficial effects of DNIC-GS were related to the transfer of [Fe(NO)2] cores to thiol groups of myocardial proteins to form intracellular DNIC pools. The study concluded that DNIC-GS is a promising adjunct agent for metabolic and antioxidant protection of the heart during cardioplegic arrest and reperfusion.

Keywords

Dinitrosyl iron complexes Isolated rat heart Cardiac function recovery Myocardial energy state ROS Membrane integrity 

Notes

Acknowledgements

The authors are grateful to Dr. V. Shulzhenko for conducting experiments on isolated perfused rat hearts.

Authors’ contributions

IS and OP designed and planned the study. AT carried out EPR experiments and EPR spectroscopy analyses. OV determined LDH activity in myocardial effluents and performed the statistical analyses. IS carried out determination of metabolites. OP, IS, and AT wrote the manuscript. All authors read, edited, and approved the final manuscript.

Funding

This work was supported by the Russian Foundation for Basic Research (grant No. 15-04-00359).

Compliance with ethical standards

The care and use of the animals were conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and other Scientific Purposes (no. 123 of March 18, 1986).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures were approved by the Bioethical Committee for Animal Care of the National Medical Research Center for Cardiology (permission no. 10 of April 25, 2017).

Supplementary material

424_2018_2251_MOESM1_ESM.doc (264 kb)
ESM 1 (DOC 263 kb)

References

  1. 1.
    Bergmeyer HU (1974) Methods of enzymatic analysis. Academic Press, New York, pp 1464–1467 1772–1776, 1777–1781, 2127–2131Google Scholar
  2. 2.
    Bergmeyer HU, Bernt E (1974) Lactate dehydrogenase. UV-assay with pyruvate and NADH. In: Methods of enzymatic analysis, 4th edn. Academic Press, New York, pp 574–578CrossRefGoogle Scholar
  3. 3.
    Britigan BE, Cohen MS, Rosen GM (1987) Detection of the production of oxygen-centered free radicals by human neutrophils using spin trapping techniques: a critical perspective. J Leukoc Biol 41:349–362CrossRefGoogle Scholar
  4. 4.
    Chazov EI, Rodnenkov OV, Zorin AV, Lakomkin VL, Gramovich VV, Vyborov ON, Dragnev AG, Timoshin AA, Buryachkovskaya LI, Abramov AA, Massenko VP, Arzamastsev EV, Kapelko VI, Vanin AF (2012) Hypotensive effect of oxacom containing a dinitrosyl iron complex with glutathione: animal studies and clinical trials on healthy volunteers. Nitric Oxide Biol Chem 26:148–156.  https://doi.org/10.1016/j.niox.2012.01.008
  5. 5.
    Clancy RM, Levartovsky D, Leszczynska-Piziak J, Yegudin J, Abramson SB (1994) Nitric oxide reacts with intracellular glutathione and activates the hexose monophosphate shunt in human neutrophils: evidence for S-nitrosoglutathione as a bioactive intermediary. Proc Natl Acad Sci U S A 91:3680–3684CrossRefGoogle Scholar
  6. 6.
    Colagrande L, Formica F, Porta F, Martino A, Sangalli F, Avalli L, Paolini G (2006) Reduced cytokines release and myocardial damage in coronary artery bypass patients due to L-arginine cardioplegia supplementation. Ann Thorac Surg 81:1256–1261.  https://doi.org/10.1016/j.athoracsur.2005.10.003 CrossRefGoogle Scholar
  7. 7.
    Du ZY, Hicks M, Jansz P, Rainer S, Spratt P, Macdonald P (1998) The nitric oxide donor, diethylamine NONOate, enhances preservation of the donor rat heart. J Heart Lung Transplant 17:1113–1120Google Scholar
  8. 8.
    Giliano NY, Konevega LV, Noskin LA, Serezhenkov VA, Poltorakov AP, Vanin AF (2011) Dinitrosyl iron complexes with thiol-containing ligands and apoptosis: studies with HeLa cell culture. Nitric Oxide Biol Chem 24:151–159.  https://doi.org/10.1016/j.niox.2011.02.005. CrossRefGoogle Scholar
  9. 9.
    Goldstein S, Russo A, Samuni A (2003) Reactions of PTIO and carboxy-PTIO with NO, NO2, and O2 _. J Biol Chem 278:50949–50955.  https://doi.org/10.1074/jbc.M308317200 CrossRefGoogle Scholar
  10. 10.
    Granger DN, Kvietys PR (2015) Reperfusion injury and reactive oxygen species: the evolution of a concept. Redox Biol 6:524–551.  https://doi.org/10.1016/j.redox.2015.08.020 CrossRefGoogle Scholar
  11. 11.
    Hallstrom S, Franz M, Gasser H, Vodrazka M, Semsroth S, Losert UM, Haisjacki M, Podesser BK, Malinski T (2008) S-nitroso human serum albumin reduces ischaemia/reperfusion injury in the pig heart after unprotected warm ischaemia. Cardiovasc Res 77:506–514.  https://doi.org/10.1093/cvr/cvm052 CrossRefGoogle Scholar
  12. 12.
    Handy DE, Loscalzo J (2006) Nitric oxide and posttranslational modification of the vascular proteome: S-nitrosation of reactive thiols. Arterioscler Thromb Vasc Biol 26:1207–1214.  https://doi.org/10.1161/01.ATV.0000217632.98717.a0 CrossRefGoogle Scholar
  13. 13.
    Johnson IIIG, Tsao PS, Lefer AM (1991) Cardioprotective effects of authentic nitric oxide in myocardial ischemia with reperfusion. Crit Care Med 19:244–252CrossRefGoogle Scholar
  14. 14.
    Kapelko VI, Lakomkin VL, Abramov AA, Lukoshkova EV, Undrovinas NA, Khapchaev AY, Shirinsky VP (2017) Protective effects of dinitrosyl iron complexes under oxidative stress in the heart. Oxid Med Cell Long, Article ID 9456163.  https://doi.org/10.1155/2017/9456163
  15. 15.
    Kawahara K, Takase M, Yamauchi Y (2003) Increased vulnerability to ischemia/reperfusion-induced ventricular tachyarrhythmias by pre-ischemic inhibition of nitric oxide synthase in isolated rat hearts. Cardiovas Pathol 12:49–56.  https://doi.org/10.1016/S1054-8807(02)00155-2 CrossRefGoogle Scholar
  16. 16.
    Kim YM, Chung HN, Simmons RL, Billar TL (2000) Cellular non-heme-iron content is a determinant of nitric oxide-mediated apoptosis, necrosis, and caspase inhibition. J Biol Chem 275:10954–10961CrossRefGoogle Scholar
  17. 17.
    Kruzliak P, Pechanova KT (2014) New perspectives of nitric oxide donors in cardiac arrest and cardiopulmonary resuscitation treatment. Heart Fail Rev 19:383–390.  https://doi.org/10.1007/s10741-013-9397-4 CrossRefGoogle Scholar
  18. 18.
    Kuppusamy P, Zwier JL (1989) Characterization of free-radical generation by xanthine oxidase. Evidence for hydroxyl radical generation. J Biol Chem 264:9880–9884Google Scholar
  19. 19.
    Mayers I, Salas E, Hurst T, Johnson D, Radomski MW (1999) Increased nitric oxide synthase activity after canine cardiopulmonary bypass is suppressed by S-nitrosoglutathione. J Thorac Cardiovasc Surg 117:1009–1016.  https://doi.org/10.1016/S0022-5223(99)70383-1 CrossRefGoogle Scholar
  20. 20.
    Pisarenko OI, Tskitishvili OV, Studneva IM, Serebryakova LI, Timoshin AA, Ruuge EK (1997) Metabolic and antioxidant effects of R(-)-N6-(2-phenylisopropyl) adenosine following regional ischemia and reperfusion in canine myocardium. Biochim Biophys Acta 1361:295–303CrossRefGoogle Scholar
  21. 21.
    Pisarenko OI, Lankin VZ, Konovalova GG, Serebryakova LI, Shulzhenko VS, Timoshin AA, Tskitishvili OV, Pelogeykina YA, Studneva IM (2014) Apelin-12 and its structural analogue enhance antioxidant defense in experimental myocardial ischemia and reperfusion. Mol Cell Biochem 391:241–250.  https://doi.org/10.1007/s11010-014-2008-4 CrossRefGoogle Scholar
  22. 22.
    Pisarenko OI, Shulzhenko VS, Pelogeykina YA, Studneva IM (2015) Enhancement of crystalloid cardioplegic protection by structural analogs of apelin-12. J Surg Res 194(1):18–24.  https://doi.org/10.1016/j.jss.2014.11.007 CrossRefGoogle Scholar
  23. 23.
    Podesser BK, Hallstrom S (2007) Nitric oxide homeostasis as a target for drug additives to cardioplegia. Br J Pharmacol 151:930–940.  https://doi.org/10.1038/sj.bjp.0707272 CrossRefGoogle Scholar
  24. 24.
    Remizova MI, Kochetygov NI, Gerbout KA, Lakomkin VL, Timoshin AA, Burgova EN, Vanin AF (2011) Effect of dinitrosyl iron complexes with glutathione on hemorrhagic shock followed by saline treatment. Eur J Pharmacol 662:40–46.  https://doi.org/10.1016/j.ejphar.2011.04.046 CrossRefGoogle Scholar
  25. 25.
    Shumaev KB, Gubkin AA, Serezhenkov VA, Lobysheva II, Kosmachevskaya OV, Ruuge EK, Lankin VZ, Topunov AF, Vanin AF (2008) Interaction of reactive oxygen and nitrogen species with albumin- and methemoglobin-bound dinitrosyl-iron complexes. Nitric Oxide Biol Chem 18:37–46.  https://doi.org/10.1016/j.niox.2007.09.085 CrossRefGoogle Scholar
  26. 26.
    Sun J, Morgan M, Shen RF, Steenbergen C, Murphy E (2007) Preconditioning results in S-nitrosylation of proteins involved in regulation of mitochondrial energetics and calcium transport. Circ Res 101:1155–1163.  https://doi.org/10.1161/CIRCRESAHA.107.155879 CrossRefGoogle Scholar
  27. 27.
    Timoshin AA, Pisarenko OI, Lakomkin VL, Studneva IM, Ruuge EK (2000) Free radical intermediates in isolated rat heart during perfusion, ischemia, and reperfusion: effect of ischemic preconditioning. Exp Clinic Cardiol 5:59–64Google Scholar
  28. 28.
    Timoshin AA, Pisarenko OI, Tskitishvili OV, Serebriakova LI, Studneva IM, Drobotova DI, Ruuge EK, Vanin AF (2010) Dinitrosyl iron complexes with glutathione in rat myocardial tissue during regional ischemia and postischemic reperfusion. Biofizika (Russian) 55(6):1099–1107Google Scholar
  29. 29.
    Timoshin AA, Lakomkin VL, Drobotova DI, Ruuge EK, Vanin AF (2013) Transformations of dinitrosyl iron complexes in an isolated rat heart after introduction of this substance into perfusion medium. Biofizika (Russian) 58:281–288Google Scholar
  30. 30.
    Tosaki A, Blasig IE, Pali T, Ebert B (1990) Heart protection and radical trapping by DMPO during reperfusion in isolated working rat hearts. Free Radic Biol Med 8:363–372CrossRefGoogle Scholar
  31. 31.
    Vanin AF (2009) Dinitrosyl iron complexes with thiolate ligands: physico-chemistry, biochemistry and physiology. Nitric Oxide Biol Chem 21:1–13.  https://doi.org/10.1016/j.niox.2009.03.005 CrossRefGoogle Scholar
  32. 32.
    Vasquez-Vivar J, Kalyanaraman B, Martasek P, Hogg N, Masters BSS, Karoui H, Tordo P, Pritchard KA (1998) Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci U S A 95:9220–9225CrossRefGoogle Scholar
  33. 33.
    Webb A, Bond ML, Uppal R, Benjamin N, Ahluwalia A (2004) Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia–reperfusion damage. PNAS 101(37):13683–13688.  https://doi.org/10.1073/pnas.0402927101 CrossRefGoogle Scholar
  34. 34.
    Yamashiro S, Noguchi K, Kuniyoshi Y, Koja K, Sakanashi M (2003) Role of tetrahydrobiopterin on ischemia–reperfusion injury in isolated perfused rat hearts. J Cardiovasc Surg 44:37–49Google Scholar
  35. 35.
    Yamashita M, Schmid RA, Ando K, Cooper JD, Patterson GA (1996) Nitroprusside ameliorates lung allograft injury. Ann Thorac Surg 62:791–796CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory for Myocardial MetabolismNational Medical Research Center for CardiologyMoscowRussian Federation

Personalised recommendations