Skip to main content

Elevation of serum lipid peroxide level associated with doxorubicin toxicity and its amelioration by [dl]-α-tocopheryl acetate or coenzyme Q10 in mouse (doxorubicin, toxicity, lipid peroxide, tocopherol, coenzyme Q10)

Summary

Elevations of serum lipid peroxide levels were demonstrated in mice after an equitoxic dose of doxorubicin. When BDF1 mice were injected with doxorubicin (20 mg/kg body weight, IP), lipid peroxide levels in sera were elevated 1 day after the injection and the levels declined on subsequent days. 5-Fluorouracil (400 mg/kg body weight, IP) never changed the peroxide levels in serum. Furthermore, it was found that the co-administration of [dl]-α-tocopheryl acetate or coenzyme Q10 IM strongly inhibited the doxorubicin-induced elevation of lipid peroxides in serum.

The effectiveness of [dl]α-tocopheryl acetate or coenzyme Q10 in reducing the lethality of doxorubicin in mice was also confirmed.

These results indicate that the measurement of serum 2-thiobarbituric acid-reacting substances provides a useful measurement of lipid peroxide levels, a useful measurement of lipid peroxide levels, which may be involved in some way with doxorubicin toxicity, and that the administration of antioxidants provide protection against some of the side effects of doxorubicin.

This is a preview of subscription content, access via your institution.

References

  1. Bertazzoli, C., Ghione, M.: Adriamycin-associated cardiotoxicity: Research on prevention with coenzyme Q. Pharmacol. Res. Commun. 9, 235–250 (1977)

    Google Scholar 

  2. Blum, R. H., Carter, S. K.: Adriamycin — A new anticancer drug with significant clinical activity. Ann. Intern. Med. 80, 249–259 (1974)

    Google Scholar 

  3. Bonadonna, G., Monfardini, S., de Lena, M., Fossati-Bellani, F., Beretta, G.: Phase I and preliminary phase II evaluation of adriamycin (NSC-123127). Cancer Res. 30, 2572–2582 (1970)

    Google Scholar 

  4. Carter, S. K.: Adriamycin — A review. J. Natl. Cancer Inst. 55, 1265–1274 (1975)

    Google Scholar 

  5. DiMarco, A., Gaetoni, M., Scarpinato, B.: Adriamycin (NSC-123127): A new antibiotic with antitumor activity. Cancer Chemother. Rep. 53, 33–37 (1969)

    Google Scholar 

  6. Gallo-Torres, H. E.: Obligatory role of bile for the intestinal absorption of vitamin E. Lipids 5, 379–384 (1970)

    Google Scholar 

  7. Goodman, J., Hochstein, P.: Generation of free radicals and lipid peroxidation by redox cycling of adriamycin and daunomycin. Biochem. Biophys. Res. Commun. 77, 797–803 (1977)

    Google Scholar 

  8. Handa, K., Sato, S.: Generation of free radicals of quinone group-containing anticancer chemicals in NADPH-microsome system, as evidenced by initiation of sulfite oxidation. Gann 66, 43–47 (1975)

    Google Scholar 

  9. Iwamoto, Y., Hansen, I. L., Porter, T. H., Folkers, K.: Inhibition of coenzyme Q10-enzymes, succinoxidase and NADH-oxidase, by adriamycin and other quinones having antitumor activity. Biochem. Biophys. Res. Commun. 58, 633–638 (1974)

    Google Scholar 

  10. Jaenke, R. S.:An anthracycline antibiotic-induced cardiomyopathy in rabbits. Lab. Invest. 30, 292–304 (1974)

    Google Scholar 

  11. Lefpak, E. A., Pitha, J., Rosenheim, S., Gottlieb, J. A.: A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32, 302–314 (1974)

    Google Scholar 

  12. Lenaz, L., Page, J. A.: Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat. Rev. 3, 111–120 (1976)

    Google Scholar 

  13. Mettler, F. P., Young, D. M., Ward, J. M.: Adriamycin-induced cardiotoxicity (cardiomyopathy and congestive heart failure) in rats. Cancer Res. 37, 2705–2713 (1977)

    Google Scholar 

  14. Myers, C. E., McGuire, W. P., Liss, R. H., Ifrim, I., Grotzinger, K., Young, R. C.: Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science 197, 165–167 (1977)

    Google Scholar 

  15. Myers, C. E., McGuire, W. P., Young, R.: Adriamycin: Amelioration of toxicity by α-tocopherol. Cancer Treat. Rep. 60, 961–962 (1976)

    Google Scholar 

  16. Oki, T., Matsuzawa, Y., Yoshimoto, A., Numata, K., Kitamura, I., Hori, S., Takamatsu, A., Umezawa, H., Ishizuka, M., Naganawa, H., Suda, H., Hamada, M., Takeuchi, T.: New antibiotics, aclacinomycin A and B. J. Antibiot. (Tokyo) 28, 830–834 (1975)

    Google Scholar 

  17. rosenoff, S. H., Brooks, E., Bostick, f., Young, R. C.: Alteration in DNA synthesis in cardiac tissue induced by adriamycin in vivo-relation to fatal toxicity. Biochem. Pharmacol. 24, 1898–1901 (1971)

    Google Scholar 

  18. Rosenoff, S. H., Olson, H. M., Young, D. M., Bostick, F., Young, R. C.: Adriamycin-induced cardiac damage in the mouse: A small-animal model of cardiotoxicity. J. Natl. Cancer Inst. 55, 191–194 (1975)

    Google Scholar 

  19. Slater, T. F.: Free radical mechanisms in tissue injury, pp. 49–61. London: Pion 1972

    Google Scholar 

  20. Yagi, K.: A simple fluorometric assay for lipoperoxide in blood plasma. Biochem. Med. 15, 212–216 (1976)

    Google Scholar 

  21. Yamanaka, N., Kato, T., Nishida, K., Ota, K.: Enhancement of DNA chain breakage by bleomycin A2 in the presence of microsomes and reduced nicotinamide adenine dinucleotide phosphate. Cancer Res. 38, 3900–3903 (1978)

    Google Scholar 

  22. Young, D. M.: Pathologic effects of adriamycin (NSC-123127) in experimental systems. Cancer Chemother. Rep. 6, 159–175 (1975)

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Yamanaka, N., Kato, T., Nishida, K. et al. Elevation of serum lipid peroxide level associated with doxorubicin toxicity and its amelioration by [dl]-α-tocopheryl acetate or coenzyme Q10 in mouse (doxorubicin, toxicity, lipid peroxide, tocopherol, coenzyme Q10). Cancer Chemother. Pharmacol. 3, 223–227 (1979). https://doi.org/10.1007/BF00254735

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00254735

Keywords

  • Lipid
  • Body Weight
  • Peroxide
  • Lipid Peroxide
  • Cancer Research