Biochemistry (Moscow)

, 76:1022 | Cite as

Mitochondria-targeted plastoquinone derivative SkQ1 decreases ischemia-reperfusion injury during liver hypothermic storage for transplantation

  • D. V. CherkashinaEmail author
  • I. A. Sosimchik
  • O. A. Semenchenko
  • V. V. Volina
  • A. Yu. PetrenkoEmail author


The ability of the mitochondria-targeted plastoquinone derivative 10-(6′-plastoquinonyl)decyl triphenylphosphonium (SkQ1) to decrease ischemia-reperfusion injury in isolated liver during hypothermic storage (HS) was studied. Rat liver was stored for 24 h at 4°C without or in the presence of 1 μM SkQ1 with following reperfusion for 60 min at 37°C. The presence in the storage medium of SkQ1 significantly decreased spontaneous production of reactive oxygen species and intensity of lipid peroxidation in the liver during HS and reperfusion. The GSH level after HS in solution with SkQ1 was reliably higher, but reperfusion leveled this effect. At all stages of experiment the presence of SkQ1 did not prevent the decrease of antioxidant enzyme activities such as catalase, GSH peroxidase, GSH reductase, and glucose-6-phosphate dehydrogenase. The addition of SkQ1 to the storage medium improved energetic function of the liver, as was revealed in increased respiratory control index of mitochondria and ATP level. SkQ1 exhibited positive effect on the liver secretory function and morphology after HS as revealed in enhanced bile flow rate during reperfusion and partial recovery of organ architectonics and state of liver sinusoids and hepatocytes. The data point to promising application of mitochondria-targeted antioxidants for correction of the ischemia-reperfusion injury of isolated liver during long-term cold storage before transplantation.

Key words

mitochondria-targeted antioxidant SkQ1 ischemia-reperfusion injury hypothermic storage of isolated liver free radical processes respiratory activity of mitochondria 


DHR 123

dihydrorhodamine 123




glucose-6-phosphate dehydrogenase


hypothermic storage


lipid peroxidation


malonic dialdehyde


normothermic reperfusion


respiratory control index


reactive oxygen species


10-(6′-plastoquinonyl)decyl triphenylphosphonium


thiobarbituric acid


  1. 1.
    Mitchell, S. J., Churchill, T. A., Winslet, M. C., and Fuller, B. J. (1999) Cryobiology, 39, 130–137.PubMedCrossRefGoogle Scholar
  2. 2.
    Skulachev, V. P. (1999) Mol. Aspects, 20, 139–184.CrossRefGoogle Scholar
  3. 3.
    Demin, O. V., Goryanin, I. I., Kholodenko, B. N., and Westerhoff, Ch. V. (2001) Mol. Biol. (Moscow), 35, 1095–1104.CrossRefGoogle Scholar
  4. 4.
    Skulachev, V. P. (1994) Biochemistry (Moscow), 59, 1433–1436.Google Scholar
  5. 5.
    Petrenko, A. Y., Cherkashina, D. V., Somov, A. Yu., Tkacheva, E. N., Semenchenko, O. A., Lebedinsky, A. S., and Fuller, B. J. (2010) Cryobiology, 60, 293–300.PubMedCrossRefGoogle Scholar
  6. 6.
    Skulachev, V. P. (2007) Biochemistry (Moscow), 72, 1385–1396.CrossRefGoogle Scholar
  7. 7.
    Bakeeva, L. E., Barskov, I. V., and Egorov, M. V. (2008) Biochemistry (Moscow), 73, 1288–1299.CrossRefGoogle Scholar
  8. 8.
    Petrenko, O. Iu., Sosimchyk, I. O., Cherkashyna, D. V., Semenchenko, O. A., and Skulachev, V. P. (2009) Ukr. Biokhim. Zh., 81, 43–48.PubMedGoogle Scholar
  9. 9.
    Somov, A. Y., Semenchenko, O. A., Green, C. J., Petrenko, A. Y., and Fuller, B. J. (2009) Cryo Lett., 30, 1–12.Google Scholar
  10. 10.
    Estabroo, R. W. (1967) in Methods in Enzymology (Estabrook, R. W., and Pulman, M. E., eds.) Academic Press, N. Y., pp. 41–47.Google Scholar
  11. 11.
    Henderso, L. M., and Chappell, J. B. (1993) Eur. J. Biochem., 217, 973–980.CrossRefGoogle Scholar
  12. 12.
    Sosimchik, I. A., Cherkashina, D. V., Somov, A. Yu., and Petrenko, A. Yu. (2009) Bull. Probl. Biol. Med., 4, 36–40.Google Scholar
  13. 13.
    Ohkawa, H., Ohishi, N., and Yagi, K. (1979) Analyt. Biochem., 95, 351–358.PubMedCrossRefGoogle Scholar
  14. 14.
    Buege, J. A., and Aust, S. D. (1978) in Methods in Enzymology (Fleisher, S., and Packer, I., eds.) Academic Press, N. Y., pp. 302–310.Google Scholar
  15. 15.
    Aebi, H. (1984) Methods Enzymol., 105, 121–127.PubMedCrossRefGoogle Scholar
  16. 16.
    Rotruck, J. T., Pope, A. L., Ganther, H. E., Swanson, A. B., Hafeman, D. G., and Hoekstra, W. G. (1973) Science, 179, 588–590.PubMedCrossRefGoogle Scholar
  17. 17.
    Carlberg, I., and Mannervik, B. (1985) Methods Enzymol., 113, 484–490.PubMedCrossRefGoogle Scholar
  18. 18.
    Rudack, D., Chisholm, E. M., and Holten, D. (1971) J. Biol. Chem., 246, 1249–1254.PubMedGoogle Scholar
  19. 19.
    Adams, H. (1963) in Methods of Enzymatic Analysis (Bergmeyer, H. U., ed.) Academic Press, N. Y., pp. 539–543.Google Scholar
  20. 20.
    Putilina, F. E. (1982) in Methods of Biochemical Investigations (Prokhorova, M. I., ed.) Leningrad State University Publishing House, Leningrad, pp. 183–185.Google Scholar
  21. 21.
    Brass, C. A., and Roberts, T. G. (1995) Gastroenterology, 108, 1167–1175.PubMedCrossRefGoogle Scholar
  22. 22.
    Shibuya, H., Ohkohchi, N., Seya, K., and Satomi, S. (1997) Hepatology, 25, 356–360.PubMedCrossRefGoogle Scholar
  23. 23.
    Cherkashina, D. V., Semenchenko, O. A., Grischuk, V. P., Fuller, B. J., and Petrenko, A. Y. (2005) Cell Preserv. Technol., 3, 203–212.CrossRefGoogle Scholar
  24. 24.
    Bailey, S. M., and Reinke, L. A. (2000) Life Sci., 66, 1033–1044.PubMedCrossRefGoogle Scholar
  25. 25.
    Jaeschke, H. (1996) J. Hepatol., 25, 774–780.PubMedCrossRefGoogle Scholar
  26. 26.
    Sewerynek, E., Reiter, R. J., Melchiorri, D., Ortiz, G. G., and Lewinski, A. (1996) Hepatogastroenterology, 43, 898–905.PubMedGoogle Scholar
  27. 27.
    Singh, I., Gulati, S., Orak, J. K., and Singh, A. K. (1993) Mol. Cell. Biochem., 125, 97–104.PubMedCrossRefGoogle Scholar
  28. 28.
    Fetisova, E. K., Avetisyan, A. V., Izyumov, D. S., Korotetskaya, M. V., Chernyak, B. V., and Skulachev, V. P. (2010) FEBS Lett., 584, 562–566.PubMedCrossRefGoogle Scholar
  29. 29.
    Roginsky, V. A., Tashlitsky, V. N., and Skulachev, V. P. (2009) Aging (Albany N. Y.), 1, 481–489.Google Scholar
  30. 30.
    Paradies, G., Petrosillo, G., Paradies, V., and Ruggiero, F. M. (2009) Cell Calcium, 45, 643–650.PubMedCrossRefGoogle Scholar
  31. 31.
    Ovsepyan, L. M., Karagezyan, K. G., Melkumyan, A. V., and Zakharyan, G. V. (2006) Doklady NAN Armenii, 4, 46–51.Google Scholar
  32. 32.
    Bindoli, A. (1988) Free Radic. Biol. Med., 5, 247–261.PubMedCrossRefGoogle Scholar
  33. 33.
    Zhang, Y., Marcillat, O., Giulivi, C., Ernster, L., and Davies, K. J. (1990) J. Biol. Chem., 265, 16330–16336.PubMedGoogle Scholar
  34. 34.
    Maevsky, E. I., Grishina, E. V., Rosenfeld, A. S., Zyakun, A. M., Vereshchagina, V. M., and Kondrashova, M. N. (2000) Biofizika, 45, 509–513.Google Scholar
  35. 35.
    Nieuwenhuijs, V. B., de Bruijn, M. T., Padbury, R. T., and Barritt, G. J. (2006) Dig. Dis. Sci., 51, 1087–1102.PubMedCrossRefGoogle Scholar
  36. 36.
    Kumamoto, Y., Suematsu, M., Shimazu, M., Kato, Y., Sano, T., Makino, N., Hirano, K. I., Naito, M., Wakabayashi, G., Ishimura, Y., and Kitajima, M. (1999) Hepatology, 30, 1454–1463.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  1. 1.Institute for Problems of Cryobiology and CryomedicineUkrainian National Academy of SciencesKharkovUkraine

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