Biochemistry (Moscow)

, Volume 74, Issue 3, pp 301–307 | Cite as

Dihydroquercetin (taxifolin) and other flavonoids as inhibitors of free radical formation at key stages of apoptosis

  • Yu. A. VladimirovEmail author
  • E. V. Proskurnina
  • E. M. Demin
  • N. S. Matveeva
  • O. B. Lubitskiy
  • A. A. Novikov
  • D. Yu. Izmailov
  • A. N. Osipov
  • V. P. Tikhonov
  • V. E. Kagan


Formation of free radicals in mitochondria plays a key role in the development of apoptosis, which includes formation of superoxide by the respiratory chain, formation of radicals by cytochrome c-cardiolipin complex in the presence of hydrogen peroxide or lipids, and chain lipid peroxidation resulting in cytochrome c release from mitochondria and initiation of the apoptotic cascade. In this work the effect of taxifolin (dihydroquercetin) and some other antioxidants on these three radical-producing reactions was studied. Peroxidase activity of the complex of cytochrome c with dioleyl cardiolipin estimated by chemiluminescence with luminol decreased by 50% with quercetin, taxifolin, rutin, Trolox, and ionol at concentrations 0.7, 0.7, 0.8, 3, and 10 μM, respectively. The lipid radical production detected by coumarin C-525-activated chemiluminescence decreased under the action of rutin and taxifolin in a dose-dependent manner, so that a 50% inhibition of chemiluminescence was observed at the antioxidant concentrations of 3.7 and 10 μM, respectively. Thus, these two radical-producing reactions responsible for apoptosis onset are inhibited by antioxidants at rather low concentrations. Experiments performed on liver slices and mash showed that taxifolin, quercetin, naringenin, and Trolox have low inhibitory effect on the lucigenin-dependent chemiluminescence in the tissue only at concentrations higher than 100 μM.

Key words

dihydroquercetin antioxidants apoptosis free-radical reactions cytochrome c cardiolipin 



bovine cardiolipin



coumarin C-525



dihydroquercetin (taxifolin)


nitric oxide


superoxide dismutase


1,1′,2,2′-tetraoleyl cardiolipin (sodium salt)


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kern, J. C., and Kehrer, J. P. (2005) Front. Biosci., 10, 1727–1738.PubMedCrossRefGoogle Scholar
  2. 2.
    Fehrenbach, E., and Northoff, H. (2001) Exerc. Immunol. Rev., 7, 66–89.PubMedGoogle Scholar
  3. 3.
    Raha, S., and Robinson, B. H. (2001) Am. J. Med. Genet., 106, 62–70.PubMedCrossRefGoogle Scholar
  4. 4.
    Lipton, S. A., and Nicotera, P. (1998) Cell Calcium, 23, 165–171.PubMedCrossRefGoogle Scholar
  5. 5.
    Stoian, I., Oros, A., and Moldoveanu, E. (1996) Biochem. Mol. Med., 59, 93–97.PubMedCrossRefGoogle Scholar
  6. 6.
    Wood, K. A., and Youle, R. J. (1994) Ann. N. Y. Acad. Sci., 738, 400–407.PubMedCrossRefGoogle Scholar
  7. 7.
    Nomura, K., Imai, H., Koumura, T., Kobayashi, T., and Nakagawa, Y. (2000) Biochem. J., 351, 183–193.PubMedCrossRefGoogle Scholar
  8. 8.
    Petrosillo, G., Ruggiero, F. M., Pistolese, M., and Paradies, G. (2001) FEBS Lett., 509, 435–438.PubMedCrossRefGoogle Scholar
  9. 9.
    Nomura, K., Imai, H., Koumura, T., Arai, M., and Nakagawa, Y. (1999) J. Biol. Chem., 274, 29294–29302.PubMedCrossRefGoogle Scholar
  10. 10.
    Kagan, V. E., Tyurin, V. A., Jiang, J., Tyurina, Y. Y., Ritov, V. B., Amoscato, A. A., Osipov, A. N., Belikova, N. A., Kapralov, A. A., Kini, V. V., Vlasova, I. I., Zhao, Q., Zou, M., Di, P., Svistunenko, D. A., Kurnikov, I. V., and Borisenko, G. G. (2005) Nature Chem. Biol., 1, 223–232.CrossRefGoogle Scholar
  11. 11.
    Lenaz, G. (1998) Biochim. Biophys. Acta, 1366, 53–67.PubMedCrossRefGoogle Scholar
  12. 12.
    Schapira, A. H. (1999) Biochim. Biophys. Acta, 1410, 159–170.PubMedCrossRefGoogle Scholar
  13. 13.
    Tatton, W. G., and Olanow, C. W. (1999) Biochim. Biophys. Acta, 1410, 195–213.PubMedCrossRefGoogle Scholar
  14. 14.
    Hunter, A. M., LaCasse, E. C., and Korneluk, R. G. (2007) Apoptosis, 12, 1543–1568.PubMedCrossRefGoogle Scholar
  15. 15.
    Lopez-Beltran, A., Maclennan, G. T., de la Haba-Rodriguez, J., Montironi, R., and Cheng, L. (2007) Anal. Quant. Cytol. Histol., 29, 71–78.PubMedGoogle Scholar
  16. 16.
    Prabhudesai, S. G., Rekhraj, S., Roberts, G., Darzi, A. W., and Ziprin, P. (2007) J. Surg. Oncol., 96, 77–88.PubMedCrossRefGoogle Scholar
  17. 17.
    Cai, S. X., Drewe, J., and Kasibhatla, S. (2006) Curr. Med. Chem., 13, 2627–2644.PubMedCrossRefGoogle Scholar
  18. 18.
    Fulda, S., and Debatin, K. M. (2006) Oncogene, 25, 4798–4811.PubMedCrossRefGoogle Scholar
  19. 19.
    Gardner, C. R. (2004) Expert Rev. Anticancer Ther., 4, 1157–1177.PubMedCrossRefGoogle Scholar
  20. 20.
    Vinogradov, A. D., and Grivennikova, V. G. (2005) Biochemistry (Moscow), 70, 120–127.CrossRefGoogle Scholar
  21. 21.
    Vladimirov, Yu. A. (1998) Vestn. Ros. Akad. Med. Nauk, 7, 43–51.Google Scholar
  22. 22.
    Kagan, V. E., Borisenko, G. G., Tyurina, Y. Y., Tyurin, V. A., Jiang, J., Potapovich, A. I., Kini, V., Amoscato, A. A., and Fujii, Y. (2004) Free Rad. Biol. Med., 37, 1963–1985.PubMedCrossRefGoogle Scholar
  23. 23.
    Belikova, N. A., Vladimirov, Y. A., Osipov, A. N., Kapralov, A. A., Tyurin, V. A., Potapovich, M. V., Basova, L. V., Peterson, J. P., Kurnikov, I. V., and Kagan, V. E. (2006) Biochemistry, 45, 4998–5009.PubMedCrossRefGoogle Scholar
  24. 24.
    Vladimirov, Yu. A. (2002) Biol. Membr. (Moscow), 19, 356–377.Google Scholar
  25. 25.
    Vladimirov, Y. A., Olenev, V. I., Suslova, T. B., and Cheremisina, Z. P. (1980) Adv. Lipid Res., 17, 173–249.PubMedGoogle Scholar
  26. 26.
    Vladimirov, Y. A. (1987) in Physicochemical Aspects of Medicine. Reviews. Soviet Medical Reviews, Section B (Lopukhin, Y. M., ed.) Harwood Academic Publishers GmbH, London, pp. 51–127.Google Scholar
  27. 27.
    Vladimirov, Y. A. (1986) in Free Radicals, Aging, and Degenerative Diseases (Johnson, J. E., Jr., Walford, R., Harman, D., and Miquel, J., eds.) Allan R. Liss, Inc., New York, pp. 141–195.Google Scholar
  28. 28.
    Vladimirov, I. A. (1998) Vestn. Ros. Akad. Med. Nauk, 7, 43–51.Google Scholar
  29. 29.
    Matveeva, N. S., Lyubitsky, O. B., Osipov, A. N., and Vladimirov, Yu. A. (2007) Biophysics (Moscow), 52, 632–639.Google Scholar
  30. 30.
    Dawson, R. M. C., Elliott, D. C., Elliott, W. H., and Jones, K. M. (1986) Data for Biochemical Research, 3rd Edn., Oxford University Press.Google Scholar
  31. 31.
    Vladimirov, Yu. A., Proskurnina, E. V., Izmailov, D. Yu., Novikov, A. A., Brusnichkin, A. V., Osipov, A. N., and Kagan, V. E. (2006) Biochemistry (Moscow), 71, 989–997.CrossRefGoogle Scholar
  32. 32.
    Vladimirov, Y. A., Sharov, V. S., Driomina, E. S., Reznitchenko, A. V., and Gashev, S. B. (1995) Free Rad. Biol. Med., 18, 739–745.PubMedCrossRefGoogle Scholar
  33. 33.
    Vladimirov, Y. A., Arroyo, A., Taylor, J. M., Tyurina, Y. Y., Matsura, T., Tyurin, V. A., and Kagan, V. E. (2000) Arch. Biochem. Biophys., 384, 154–162.PubMedCrossRefGoogle Scholar
  34. 34.
    Brown, G. C., and Borutaite, V. (1999) Biochem. Soc. Symp., 66, 17–25.PubMedGoogle Scholar
  35. 35.
    Salgo, M. G., and Pryor, W. A. (1996) Arch. Biochem. Biophys., 333, 482–488.PubMedCrossRefGoogle Scholar
  36. 36.
    Ischiropoulos, H. (1998) Am. J. Physiol., 274, C853–C854.PubMedGoogle Scholar
  37. 37.
    Klimek, J. (1988) Biochim. Biophys. Acta, 958, 31–39.PubMedGoogle Scholar
  38. 38.
    Liang, L. P., and Patel, M. (2004) J. Neurochem., 90, 1076–1084.PubMedCrossRefGoogle Scholar
  39. 39.
    Liochev, S. I., and Fridovich, I. (1997) Free Rad. Biol. Med., 23, 668–671.PubMedCrossRefGoogle Scholar
  40. 40.
    Vladimirov, Yu. A., Proskurnina, E. V., Izmailov, D. Yu., Novikov, A. A., Brusnichkin, A. V., Osipov, A. N., and Kagan, V. E. (2006) Biochemistry (Moscow), 71, 998–1005.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2009

Authors and Affiliations

  • Yu. A. Vladimirov
    • 1
    Email author
  • E. V. Proskurnina
    • 1
  • E. M. Demin
    • 1
  • N. S. Matveeva
    • 2
  • O. B. Lubitskiy
    • 2
  • A. A. Novikov
    • 2
  • D. Yu. Izmailov
    • 1
  • A. N. Osipov
    • 2
  • V. P. Tikhonov
    • 3
  • V. E. Kagan
    • 4
  1. 1.Faculty of Basic MedicineLomonosov Moscow State UniversityMoscowRussia
  2. 2.Russian State Medical UniversityMoscowRussia
  3. 3.Moscow Plant “Diod”MoscowRussia
  4. 4.University of PittsburghPittsburghUSA

Personalised recommendations