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Effect of amrinone on anthracycline-induced lethal and cardiac toxicity in mice and rats

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The protective role of amrinone against toxicity of anthracyclines was examined in both mice and rats. These two anthracyclincs were selected since they are characterized by different patterns of toxicity. In contrast to doxorubicin, the 4′-deoxy derivative did not cause delayed mortality. The results of this investigation indicate that amrinone is an effective protective agent against acute lethal events induced by both anthracyclines. However, the inotropic agent did not reduce the delayed mortality produced by doxorubicin. This parallels the apparent lack of prevention of doxorubicin-induced myocardial toxicity in CD rats, as determined by ECG changes and by morphologic alterations following multiple drug administrations. The administration of amrinone did not interfere with the antitumor activity of 4′-deoxy-doxorubicin against C-26 colon tumor.

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  1. 1.

    Carter S K: The clinical evaluation of analogs — III. Anthracyclines.Cancer Chemother Pharmacol 4, 5 (1980).

  2. 2.

    Unverferth D V, Magorien R D, Leier C V, Balcer-zak S P: Doxorubicin cardiotoxicity.Cancer Treat Rev 9, 149 (1982).

  3. 3.

    Olson R D, Boerth R C, Gerber J G, Nies A S: Mechanism of adriamycin cardiotoxicity: evidence for oxidative stress.Life Sci 29, 1393 (1981).

  4. 4.

    Doroshow J H: Effect of anthracycline antibiotics on oxygen radical formation in rat heart.Cancer Res 43, 460 (1983).

  5. 5.

    Farah A E, Alousi A A, Schwarz, R P Jr: Positive inotropic agents.Ann Rev Pharmacol Toxicol 24, 275 (1984).

  6. 6.

    Bossa R, Galatulas I, Savi G, Supino R, Zunino F: Reduction of lethal toxicity of doxorubicin by amrinone.Tumori 68, 499 (1982).

  7. 7.

    Casazza A M, Savi G, Pratesi G, Di Marco A: Antitumor activity in mice of 4′-deoxydoxorubicin in comparison with doxorubicin.Eur J Cancer clin Oncol 19, 411 (1983).

  8. 8.

    Arcamone F: Antitumor anthracyclines: recent developments.Med Res Rev 4, 153 (1984).

  9. 9.

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

  10. 10.

    Villani F, Monti E, Favalli L, Lanza E, Poggi P: A model of doxorubicin-induced cardiomyopathy in the rat.IRCS med Sci 14, 282 (1986).

  11. 11.

    Beinfield W H, Lehr D: QRS-T variations in the rat electrocardiogram.Am J Physiol 214, 197 (1968).

  12. 12.

    Buschmann G, Schumaker R, Budden R, Küle U: Evaluation of the effect of dopamine and other catecholamines on the electrocardiogram and blood pressure of rats by means of on-line biosignal processing.J cardiovase Pharmacol 2, 777 (1980).

  13. 13.

    Jensen R A, Acton E M, Peters J H: Doxorubicin cardiotoxicity in the rat: comparison of ECG, trans-membrane potential and structure effects.J cardio-vase Pharmacol 6, 186 (1984).

  14. 14.

    Bossa, R, Galatulas I, Savi G, Supino R, Zunino F: Reduction of lethal toxicity of doxorubicin by amrinone.Proc 13th Int Congr Chemother, Vienna, Abstract Ps 12.4.14 (28 August–2 September 1983).

  15. 15.

    Giuliani F C, Spreafico F, Casazza A M: Preclinical studies on new anthracyclines: antitumor, toxicologic and pharmacologie properties, in Hansen H H (ed):Anthracyclines and Cancer Therapy, pp. 192–208. Amsterdam, Excerpta Medica (1983).

  16. 16.

    Maral R J, Jouanne M: Toxicology of daunorubicin in animals and man.Cancer Treat Rep 65, 9 (1981).

  17. 17.

    Rosenoff S H, Olson H M, Young D M, Bostick F, Young R C: Brief communication: adriamycin-induced cardiac damage in the mouse: a small-animal model of cardiotoxicity.J natn Cancer Iust 55, 191 (1975).

  18. 18.

    Azuma J, Sperelakis N, Hasegawa H, Tanimoto T, Vogel S, Ogura K, Awata N, Sawamura A, Harada H, Ishiyama T, Morita Y, Yamamura Y: Adriamycin cardiotoxicity: possible pathogenic mechanisms.J mol cell Cardiol 13, 381 (1981).

  19. 19.

    Formelli F, Pollini C, Casazza A M, Di Marco A, Mariani A: Fluorescence assay and pharmacokinetic studies of 4′-Deoxydoxorubicin in organs of mice bearing solid tumors.Cancer Chemother Pharmacol 5, 139 (1981).

  20. 20.

    Bristow M R, Wayne A, Minobe W A, Billingham M E, Marmor J B, Johnson G A, Ishimoto B S, Sageman W S, Daniels J R: Anthracycline-associated cardiac and renal damage in rabbits. Evidence for mediation by vasoactive substances.Lab Invest 45, 157 (1981).

  21. 21.

    Bristow M R, Thompson P D, Martin R P, Billingham M E, Harrison D C: Early anthracycline cardiotoxicity.Am J Med 65, 823 (1978).

  22. 22.

    Wortman J E, Lucas V S, Schuster E, Thiele D, Logue D L: Sudden death during doxorubicin administration.Cancer 44, 1588 (1979).

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Correspondence to F. Villani or C. Manzotti or M. Mella or E. Monti or G. Savi or F. Zunino.

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Villani, F., Manzotti, C., Mella, M. et al. Effect of amrinone on anthracycline-induced lethal and cardiac toxicity in mice and rats. Med. Oncol. & Tumor Pharmacother. 7, 227–232 (1990). https://doi.org/10.1007/BF02987100

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Key words

  • Anthracyclines
  • Amrinone
  • Lethal toxicity
  • Cardiotoxicity