Protection of peroxynitrite-induced DNA damage by dietary antioxidants

Articles Drug Development

Abstract

The present study was undertaken to test the hypothesis that dietary antioxidants protect DNA damage induced by peroxynitrite, a potent physiological inorganic toxin. The present study showed that dietary antioxidants such as (−)-epigallocatechin, gallate, quercerin, rutin, resveratrol, and ursolic acid inhibit single strand breaks in supercoiled plasmid DNA induced by 3-morpholinosyndromine N-ethylcarbamide (SIN-1), a generator of peroxynitrite, through the reaction between nitric oxide and superoxide anion. The formation of 8-hydroxy-2′-deoxyguanosine (8-OH-dG) in calf thymus DNA by SIN-1 was also inhibited by dietary antioxidants. When U937 cells were incubated with 1 mM SIN-1 bolus, a significant increase of 8-OH-dG level was observed. However, oxidative DNA damage was significantly lower in the cells pre-treated with dietary antioxidants when cells were exposed to SIN-1.

Key words

Dietary antioxidants Peroxynitrite DNA damage 

References

  1. Afanas'ev, I. B., Dorozhko, A. I., Brodskii, A. V., Kostyuk, V. A., and Potapovitch, A. I., Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation.Biochem. Pharmacol., 38, 1763–1769 (1989).PubMedCrossRefGoogle Scholar
  2. Ames, B. N., Gold, L. S., and Willet, W. C., The causes and prevention of cancer.Proc. Natl. Acad. Sci. USA, 92, 5258–5265 (1995).PubMedCrossRefGoogle Scholar
  3. Balanehru, S. and Nagarajan, B., Protective effect of oleanolic acid and ursolic acid against lipid peroxidation.Biochem. Int., 24, 981–990 (1991).PubMedGoogle Scholar
  4. Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., and Freeman, B. A., Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide.Proc. Natl. Acad. Sci. USA, 87, 1620–1624 (1990).PubMedCrossRefGoogle Scholar
  5. Beckman, J. S., Carson, M., Smith, C. D., and Koppenol, W. H., ALS, SOD and Peroxynitrite.Nature, 364, 584 (1993).PubMedCrossRefGoogle Scholar
  6. Carreras, M. C., Pargament, G. A., Catz, S. D., Poderosa, J. J., and Boveris, A., Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respiratory burst of human neutrophils.FEBS Lett., 341, 65–68 (1994).PubMedCrossRefGoogle Scholar
  7. Galati, G. and O'Brien, P. J., Potential toxicity of flavonoids and other dietary phenolics: Significance for their chemopreventive and anticancer properties.Free Radic. Biol. Med., 37, 287–303 (2004).PubMedCrossRefGoogle Scholar
  8. Hertog, M. G., Hollman, P. C., Katan, M. B., and Kromhout, D., Intake of potentially anticarcinogenic flavonoids and their determinants in adults in The Netherlands.Nutr. Cancer. 20, 21–29 (1993).PubMedCrossRefGoogle Scholar
  9. Ischiropoulos, H., Zhu, L., and Beckman, J. S., Peroxynitrite formation from macrophage-derived nitric oxide.Arch. Biochem. Biophys., 298, 446–451 (1992).PubMedCrossRefGoogle Scholar
  10. Juedes, M. J. and Wogan, G. N., Peroxynitrite-induced mutation spectra of pSP189 following replication in bacteria and in human cells.Mut. Res., 349, 51–61 (1996).Google Scholar
  11. Kaur, H. and Halliwell, B., Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients.FEBS Lett., 350, 9–12 (1994).PubMedCrossRefGoogle Scholar
  12. Kooy, N. W. and Royall, J. A., Agonist-induced peroxynitrite production from endothelial cells.Arch. Biochem. Biophys., 310, 352–359 (1994).PubMedCrossRefGoogle Scholar
  13. Koppenol, W. H., Moreno, J. J., Pryor W. A., Ischiropoulos, H., and Beckman, J. S., Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide.Chem. Res. Toxicol., 5, 834–842 (1992).PubMedCrossRefGoogle Scholar
  14. Park, J.-W. and Floyd, R. A., Lipid peroxidation products mediate the formation of 8-hydroxydeoxyguanosine in DNA.Free Radic. Biol. Med., 12, 245–250 (1992).PubMedCrossRefGoogle Scholar
  15. Park, J.-W. and Floyd R. A., Generation of strand breaks and formation of 8-hydroxy-2′-deoxyguanosine in DNA by a thiol/Fe3+/O2-catalyzed oxidation system.Arch. Biochem. Biophys., 12, 245–250 (1992).Google Scholar
  16. Radi, R., Beckman, J. S., Bush, K. M., and Freeman, B. A., Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide.J. Biol. Chem., 266, 4244–4250 (1991).PubMedGoogle Scholar
  17. Salgo, M. G. and Pryor, W. A., Trolox inhibits peroxynitrite-mediated oxidative stress and apoptosis in rat thymocytes.Arch. Biochem. Biophys., 333, 482–488 (1996).PubMedCrossRefGoogle Scholar
  18. Shibutani, S., Takeshita, M., and Grollman, A. P., Insertion of specific base during DNA synthesis past the oxidation-damaged base 8-oxodG.Nature, 349, 431–434 (1991).PubMedCrossRefGoogle Scholar
  19. Struthers, L., Patel, R., Clark, J., and Thomas, S., Direct detection of 8-oxodeoxyguanosine and 8-oxoguanine by avidin and its analogues.Anal. Biochem., 255, 20–31 (1998).PubMedCrossRefGoogle Scholar
  20. Sun, A. Y., Simonyi, A., and Sun, G. Y., The “French paradox” and beyond: Neuroprotective effects of polyphenols.Free Radic. Biol. Med., 32, 314–318 (2002).PubMedCrossRefGoogle Scholar
  21. Sundaresan, M., Yu, Z. Y., Ferrans, C. J., Irani, K., and Finkel, T., Requirement for generation of H2O2 for platelet-derived growth factor signal transduction.Science, 270, 296–299 (1995).PubMedCrossRefGoogle Scholar

Copyright information

© The Pharmaceutical Society of Korea 2006

Authors and Affiliations

  • Hye Kyung Moon
    • 1
  • Eun Sun Yang
    • 1
  • Jeen Woo Park
    • 1
  1. 1.School of Life Sciences and Biotechnology and Agro-Biotechnology Education CenterKyungpook National UniversityTaeguKorea

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