Skip to main content
SpringerLink
Log in

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

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

DHR 123:

dihydrorhodamine 123

DNP:

2,4-dinitrophenol

G6PDH:

glucose-6-phosphate dehydrogenase

HS:

hypothermic storage

LPO:

lipid peroxidation

MDA:

malonic dialdehyde

NR:

normothermic reperfusion

RCI:

respiratory control index

ROS:

reactive oxygen species

SkQ1 :

10-(6′-plastoquinonyl)decyl triphenylphosphonium

TBA:

thiobarbituric acid

References

  1. Mitchell, S. J., Churchill, T. A., Winslet, M. C., and Fuller, B. J. (1999) Cryobiology, 39, 130–137.

    Article  PubMed  CAS  Google Scholar 

  2. Skulachev, V. P. (1999) Mol. Aspects, 20, 139–184.

    Article  CAS  Google Scholar 

  3. Demin, O. V., Goryanin, I. I., Kholodenko, B. N., and Westerhoff, Ch. V. (2001) Mol. Biol. (Moscow), 35, 1095–1104.

    Article  CAS  Google Scholar 

  4. Skulachev, V. P. (1994) Biochemistry (Moscow), 59, 1433–1436.

    Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  6. Skulachev, V. P. (2007) Biochemistry (Moscow), 72, 1385–1396.

    Article  CAS  Google Scholar 

  7. Bakeeva, L. E., Barskov, I. V., and Egorov, M. V. (2008) Biochemistry (Moscow), 73, 1288–1299.

    Article  CAS  Google Scholar 

  8. Petrenko, O. Iu., Sosimchyk, I. O., Cherkashyna, D. V., Semenchenko, O. A., and Skulachev, V. P. (2009) Ukr. Biokhim. Zh., 81, 43–48.

    PubMed  CAS  Google Scholar 

  9. Somov, A. Y., Semenchenko, O. A., Green, C. J., Petrenko, A. Y., and Fuller, B. J. (2009) Cryo Lett., 30, 1–12.

    CAS  Google Scholar 

  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. Henderso, L. M., and Chappell, J. B. (1993) Eur. J. Biochem., 217, 973–980.

    Article  Google Scholar 

  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. Ohkawa, H., Ohishi, N., and Yagi, K. (1979) Analyt. Biochem., 95, 351–358.

    Article  PubMed  CAS  Google Scholar 

  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. Aebi, H. (1984) Methods Enzymol., 105, 121–127.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  17. Carlberg, I., and Mannervik, B. (1985) Methods Enzymol., 113, 484–490.

    Article  PubMed  CAS  Google Scholar 

  18. Rudack, D., Chisholm, E. M., and Holten, D. (1971) J. Biol. Chem., 246, 1249–1254.

    PubMed  CAS  Google Scholar 

  19. Adams, H. (1963) in Methods of Enzymatic Analysis (Bergmeyer, H. U., ed.) Academic Press, N. Y., pp. 539–543.

    Google Scholar 

  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. Brass, C. A., and Roberts, T. G. (1995) Gastroenterology, 108, 1167–1175.

    Article  PubMed  CAS  Google Scholar 

  22. Shibuya, H., Ohkohchi, N., Seya, K., and Satomi, S. (1997) Hepatology, 25, 356–360.

    Article  PubMed  CAS  Google Scholar 

  23. Cherkashina, D. V., Semenchenko, O. A., Grischuk, V. P., Fuller, B. J., and Petrenko, A. Y. (2005) Cell Preserv. Technol., 3, 203–212.

    Article  Google Scholar 

  24. Bailey, S. M., and Reinke, L. A. (2000) Life Sci., 66, 1033–1044.

    Article  PubMed  CAS  Google Scholar 

  25. Jaeschke, H. (1996) J. Hepatol., 25, 774–780.

    Article  PubMed  CAS  Google Scholar 

  26. Sewerynek, E., Reiter, R. J., Melchiorri, D., Ortiz, G. G., and Lewinski, A. (1996) Hepatogastroenterology, 43, 898–905.

    PubMed  CAS  Google Scholar 

  27. Singh, I., Gulati, S., Orak, J. K., and Singh, A. K. (1993) Mol. Cell. Biochem., 125, 97–104.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  29. Roginsky, V. A., Tashlitsky, V. N., and Skulachev, V. P. (2009) Aging (Albany N. Y.), 1, 481–489.

    CAS  Google Scholar 

  30. Paradies, G., Petrosillo, G., Paradies, V., and Ruggiero, F. M. (2009) Cell Calcium, 45, 643–650.

    Article  PubMed  CAS  Google Scholar 

  31. Ovsepyan, L. M., Karagezyan, K. G., Melkumyan, A. V., and Zakharyan, G. V. (2006) Doklady NAN Armenii, 4, 46–51.

    Google Scholar 

  32. Bindoli, A. (1988) Free Radic. Biol. Med., 5, 247–261.

    Article  PubMed  CAS  Google Scholar 

  33. Zhang, Y., Marcillat, O., Giulivi, C., Ernster, L., and Davies, K. J. (1990) J. Biol. Chem., 265, 16330–16336.

    PubMed  CAS  Google Scholar 

  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.

    CAS  Google Scholar 

  35. Nieuwenhuijs, V. B., de Bruijn, M. T., Padbury, R. T., and Barritt, G. J. (2006) Dig. Dis. Sci., 51, 1087–1102.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute for Problems of Cryobiology and Cryomedicine, Ukrainian National Academy of Sciences, Pereyaslavskaya str. 23, 61015, Kharkov, Ukraine

    D. V. Cherkashina, I. A. Sosimchik, O. A. Semenchenko, V. V. Volina & A. Yu. Petrenko

Authors
  1. D. V. Cherkashina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. A. Sosimchik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. A. Semenchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. V. Volina
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Yu. Petrenko
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to D. V. Cherkashina or A. Yu. Petrenko.

Additional information

Original Russian Text © D. V. Cherkashina, I. A. Sosimchik, O. A. Semenchenko, V. V. Volina, A. Yu. Petrenko, 2011, published in Biokhimiya, 2011, Vol. 76, No. 9, pp. 1254–1263.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cherkashina, D.V., Sosimchik, I.A., Semenchenko, O.A. et al. Mitochondria-targeted plastoquinone derivative SkQ1 decreases ischemia-reperfusion injury during liver hypothermic storage for transplantation. Biochemistry Moscow 76, 1022–1029 (2011). https://doi.org/10.1134/S0006297911090069

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297911090069

Key words

Search

Navigation