Skip to main content
SpringerLink
Log in

Influence of selenium deficiency on the acute cardiotoxicity of adriamycin in rats

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

The influence of selenium (Se) deficiency on the acute cardiotoxicity induced by the anticancer drug adriamycin (ADR) has been studied in rats by electrocardiography.

Two categories were formed by feeding groups of rats a Se-supplemented and a Se-deficient diet. The supplemented animals were taken as normals. The two categories were treated with iv injections of saline solution containing ADR at doses of 0, 7.5, and 15 mg/kg body wt.

The cardiac Se concentration and glutathione peroxidase (GSH-Px) activity in the Se-deficient groups were <2% lower than in the normals.

The normal groups showed significant widening of the SaT and QaT durations when given 15 mg/kg ADR. The Se-deficient groups exhibited a dose-dependent widening of the SaT and QaT duration at 7.5 and 15 mg/kg and narrowing of the PQ duration at 15 mg/kg ADR. No heart rate or QRS duration changes were detected in both categories.

Our results suggest that an imbalance of the antioxidant system is associated with Se deficiency and that Se plays a role in preventing the cardiac functional disorder attributable to oxygen free radical formation induced by ADR.

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

References

  1. R. F. Burk, Protection against free radical injury by selenoenzymes,Pharmacol. Ther. 45, 383–385 (1990).

    Article  PubMed  CAS  Google Scholar 

  2. H. W. Lane, A. O. Barroso, D. Englert, S. J. Dudrick, and B. S. MacFadyen, Jr., Selenium status of seven chronic intravenous hyperalimentation patients,JPEN 6, 426–431 (1982).

    CAS  Google Scholar 

  3. S. S. Baker, R. H. Lerman, S. H. Kery, K. S. Crocker, E. F. Hirsh, and H. Cohen, Selenium deficiency with total parenteral nutrition: reversal of biochemical and functional abnormalities by selenium supplementation: a case report,Am. J. Clin. Nutr. 38, 769–774 (1983).

    PubMed  CAS  Google Scholar 

  4. S. Jacobson and L-O. Plantin, Concentration of selenium in plasma and erythrocytes during total parenteral nutrition in Crohn's disease,Gut 26, 50–54 (1985).

    Article  PubMed  CAS  Google Scholar 

  5. H. W. Lane, C. A. Lotspeich, C. E. Moore, J. Ballard, S. T. Dudrick, and D. C. Warren, The effect of selenium supplementation on selenium status of patients receiving chronic total parenteral nutrition,JPEN 11, 177–182 (1987).

    CAS  Google Scholar 

  6. H. J. Cohen, M. R. Brown, D. Hamilton, J. Lyons-Patterson, N. Avissar, and P. Liegey, Glutathione peroxidase and elenium deficiency in patients receiving home parenteral nutrition: time course for development of deficiency and repletion of enzyme activity in plasma and blood cells,Am. J. Clin. Nutr. 49, 132–139 (1989).

    PubMed  CAS  Google Scholar 

  7. K. Sando, M. Hoki, R. Nezu, Y. Takagi, and A. Okada, Platelet glutathione peroxidase activity in long-term total parenteral nutrition with and without selenium supplementation,JPEN 16, 54–58 (1992).

    CAS  Google Scholar 

  8. A. M. van Rij, C. D. Thomson, J. M. McKenzie, and M. F. Robinson, Selenium deficiency in total parenteral nutrition,Am. J. Clin. Nutr. 32, 2076–2085 (1979).

    PubMed  Google Scholar 

  9. C. L. Kien and H. E. Ganther, Manifestations of chronic selenium deficiency in a child receiving total parenteral nutrition,Am. J. Clin. Nutr. 37, 319–328 (1983).

    PubMed  CAS  Google Scholar 

  10. R. J. Baptista, B. R. Bistrian, G. L. Blackburn, D. G. Miller, C. D. Champagne, and L. Buchanan, Utilizing selenious acid to reverse selenium deficiency in total parenteral nutrition patients,Am. J. Clin. Nutr. 39, 816–820 (1984).

    PubMed  CAS  Google Scholar 

  11. R. D. Watson, R. A. Cannon, G. S. Kurland, K. L. Cox, and R. C. Frates, Selenium responsive myositis during prolonged home total parenteral nutrition in cystic fibrosis,JPEN 9, 58–60 (1985).

    CAS  Google Scholar 

  12. R. A. Johnson, S. S. Baker, J. T. Fallon, E. P. Maynard III, J. N. Ruskin, Z. Wen, K. Ge, and H. J. Cohen, An occidental case of cardiomyopathy and selenium deficiency,N. Engl. J. Med. 304, 1210–1212 (1981).

    Article  PubMed  CAS  Google Scholar 

  13. C. R. Fleming, J. T. Lie, J. T. McCall, J. F. O'Brien, E. E. Baillie, and J. L. Thistle, Selenium deficiency and fatal cardiomyopathy in a patient on home parenteral nutrition,Gastroenterology 83, 689–693 (1982).

    PubMed  CAS  Google Scholar 

  14. R. A. Quercia, S. Korn, D. O'Neill, J. E. Dougherty, M. Ludwig, R. Schweizer, and R. Sigman, Selenium deficiency and fatal cardiomyopathy in a patient receiving long-term home parenteral nutrition,Clin. Pharm. 3, 531–535 (1984).

    PubMed  CAS  Google Scholar 

  15. B. Halliwell and J. M. C. Gutteridge, Role of free radicals and catalytic metal ions in human disease: an overview, inMethods in Enzymology, vol. 186, L. Packer and A. N. Glazer, eds., Academic, San Diego, pp. 1–85 (1990).

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. P. K. Singal, C. M. R. Deally, and L. E. Weinberg, Subcellular effects of adriamycin in the heart: a concise review,J. Mol. Cell Cardiol. 19, 817–828 (1987).

    Article  PubMed  CAS  Google Scholar 

  18. C. A. Maggi and A. Meli, Suitability of urethane anesthesia for physiopharmacological investigations in various systems: 2. Cardiovascular system,Experientia 42, 292–297 (1986).

    Article  PubMed  CAS  Google Scholar 

  19. K. Sekine, M. Kimura, and Y. Itokawa, Method for the determination of selenium in biological samples by hydrogen selenide evolution electrothermal atomic absorption,Jpn. J. Hyg. 39, 807–811 (1984).

    CAS  Google Scholar 

  20. D. E. Paglia and W. N. Valentine, Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase,J. Lab. Clin. Med. 70, 158–169 (1967).

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  22. F. Villani, E. Monti, F. Piccinini, L. Favalli, E. Lanza, A. R. Dionigi, and P. Poggi, Relationship between doxorubicin-induced ECG changes and myocardial alterations in rats,Tumori 72, 323–329 (1986).

    PubMed  CAS  Google Scholar 

  23. S. T. Hu, E. Brandle, and G. Zbinden, Inhibition of cardiotoxic, nephrotoxic and neurotoxic effects of doxorubicin by ICRF-152,Pharmacology 26, 210–220 (1983).

    Article  CAS  Google Scholar 

  24. G. Zbinden and E. Brandle, Toxicologic screening of daunorubicin (NSC-82151), adriamycin (NSC-123127) and their derivatives in rats,Cancer Chemother. Rep. 59, 707–715 (1975).

    PubMed  CAS  Google Scholar 

  25. R. A. Jensen, E. M. Acton, and J. H. Peters, Doxorubicin cardiotoxicity in the rat: comparison of ECG, transmembrane potential and structural effects,J. Cardiovasc. Pharmacol. 6, 186–200 (1984).

    Article  PubMed  CAS  Google Scholar 

  26. R. A. Jensen, E. M. Acton, and J. H. Peters, Electrocardiographic and transmembrane potential effects of 5-iminodaunorubicin in the rat,Cancer Res. 44, 4030–4039 (1984).

    PubMed  CAS  Google Scholar 

  27. R. Danesi, N. Bernardini, A. Marchetti, M. Bernardini, and M. D. Tacca, Protective effects of fructose-1, 6-diphosphate on acute and chronic doxorubicin cardiotoxicity in rats,Cancer Chemother. Pharmacol. 25, 326–332 (1990).

    Article  PubMed  CAS  Google Scholar 

  28. N. Koukay, S. Mouhieddine, M. J. Richard, J. Arnaud, J. De Leiris, and A. Favier, Influence of selenium on lipid peroxidation and cardiac functions in chronically adriamycin-treated rats,Adv. Exp. Med. Biol. 264, 353–359 (1990).

    PubMed  CAS  Google Scholar 

  29. J. G. Fischer, R. L. Tackett, E. W. Howerth, and M. A. Johnson, Copper and selenium deficiencies do not enhance the cardiotoxicity in rats due to chronic doxorubicin treatment,J. Nutr. 122, 2128–2137 (1992).

    PubMed  CAS  Google Scholar 

  30. X. Chen, A. Xue, V. C. Morris, V. J. Ferrans, E. H. Herman, A. El-Hage, and O. A. Levander, Effect of selenium deficiency on the chronic toxicity of adriamycin in rats,J. Nutr. 116, 2453–2465 (1986).

    PubMed  CAS  Google Scholar 

  31. T. Facchinetti, F. Delaini, M. Salmona, M. B. Donati, S. Feuerstein, and A. Wendel, The influence of selenium intake on chronic adriamycin toxicity and lipid peroxidation in rats,Toxicol. Lett. 15, 301–307 (1983).

    Article  PubMed  CAS  Google Scholar 

  32. K. V. Dimitrov, M. B. Hay, S. Siew, D. A. Hudler, L. J. Charamella, and D. E. Ullrey, Abrogation of adriamycin-induced cardiotoxicity by selenium in rabbits.Am. J. Pathol. 126, 376–383 (1987).

    PubMed  CAS  Google Scholar 

  33. J. A. Butler, P. D. Whanger, and N. M. Patton, Effects of feeding selenium deficient diets to rhesus monkeys (macaca mulatta),J. Am. Coll. Nutr. 7, 43–56 (1988).

    PubMed  CAS  Google Scholar 

  34. Z. Zhu, M. Kimura, and Y. Itokawa, Effect of selenium and protein deficiency on selenium and glutathione peroxidase in rats,Biol. Trace Element Res. 36, 15–23 (1993).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Development Laboratories, Nippon Hoechst Marion Roussel Ltd., 1658, Ohshinohara, Yasu-cho, Yasu-gun, 520-23, Shiga, Japan

    Akihiko Matsuda

  2. Department of Social and Preventive Medicine, Kyoto University, 606-01, Kyoto, Japan

    Akihiko Matsuda & Mieko Kimura

  3. Department of International Environmental Medicine, Graduate School of Medicine, Kyoto University, 606-01, Kyoto, Japan

    Yoshinori Itokawa

Authors
  1. Akihiko Matsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mieko Kimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yoshinori Itokawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsuda, A., Kimura, M. & Itokawa, Y. Influence of selenium deficiency on the acute cardiotoxicity of adriamycin in rats. Biol Trace Elem Res 57, 157–167 (1997). https://doi.org/10.1007/BF02778199

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02778199

Index Entries

Search

Navigation