Abstract
To ascertain any differences in myocardial injury exerted by the anthracyclines doxorubicin and epirubicin, their ability to generate oxygen free radicals when mixed with Fe(II) was examined in vitro using an oxygen electrode. 5–250 μg/ml doxorubicin or epirubicin consumed oxygen when mixed with 50 or 100 μmol/1 Fe(II). Addition of 75 μmol/1 cytochrome C showed that of the consumed oxygen, approximately 80% entered the monovalent pathway of oxygen reduction. The strong inhibitory effect of 250 mg/1 catalase indicates that most of the superoxide radicals generated are further reduced to hydrogen peroxide by both anthracyclines. Addition of metal chelators DTPA (100/μmol/1), or DDTC (50 μmol/1) did not affect oxygen consumption, whereas EDTA (100/μmol/1) or desferrioxamine (100 μmol/1) with anthracyclines and Fe(II) rather stimulated oxygen consumption. It is concluded that there are no significant differences in the amount or proportion of generated oxygen free radicals between doxorubicin and epirubicin when mixed with Fe(II) in a cell-free system in vitro. Thus, the ability of the anthracyclines, in conjunction with iron alone, to generate radicals does not explain the differences of the drugs in causing myocardial injury.
References
Babson, J. R., Abell, N. S. and Reed, D. J. (1981).Biochem. Pharmacol. 30:2299–2304.
Bachur, N. R., Gordon, S. L. and Gee, M. V. (1977).Mol. Pharmacol 13:901–910.
Bachur, N. R., Gordon, S. L. and Gee, M. V. (1978).Cancer Res. 38:1745–1750.
Ballet, F., Robert, J., Bouma, M. E., Vrignaud, P. and Infante, R. (1986).Pharmacol. Res. Commun. 18:343–347.
Berlin, V. and Hazeltine, W. A. (1981).J. Biol. Chem. 256:4747–4756.
Bozzi, A., Mavelli, I., Mondovi, B., Strom, R. and Rotilo, G. (1981).Biochem. J. 194:369–372.
Ganzine, F. (1983).Cancer Treat. Rev. 10:1–22.
Herman, E. H., Ferrans, V. J., Myers, C. E. and van Vleet, J. F. (1985).Cancer Res. 45:276–281.
von Hoff, D. D., Layartd, M. W., Basa, P., Davis, H. L., Rozencweig, M. and Muggia, F. M. (1979).Ann. Intern. Med. 91:710.
Marklund, S. and Marklund, G. (1974).Eur. J. Biochem. 47:469–474.
McGinnes, J. E., Proctor, P. H., Demopoulos, H. B., Hokanson, J. A. and Van, N. T. (1979). In:Proceedings of the Conference on Activated Oxygen and Medicine, Hawaii.
Muindi, J., Sinha, B. K., Gianni, L. and Myers, C. (1985).Mol., Pharmacol. 27:356–365.
Myers, C. E., McGuire, W. P., Liss, R. H., Ifrim, I., Grotzinger, K. and Young, R. C. (1977).Science 197:165–167.
Myers, C., Gianni, L., Zweier, J., Muindi, J., Sinha, B. K. and Eliot, H. (1986).Fed. Proc. 45:2792–2797.
Myers, C. E., Gianni, L., Simone, C. B., Klecker, R. and Greene, R. (1982).Biochemistry 21:1707–1713.
Olson, R. D., MacDonald, J. S., Harbison, R. D., van Boxtel, C. J., Boerth, R. C., Slonim, A. E. and Oates, J. A. (1977).Fed. Proc. 36:303.
Revis, N. W. and Marusic, N. (1978).J. Mol. Cell. Cardiol. 10:945–951.
Samejima, A. and Yang, J. T. (1963).J. Biol. Chem. 238:3256–3261.
Schinetti, M. L., Rossini, J. D. and Bertelli, A. (1987).J. Cancer Res. Clin. Oncol. 113:15–19.
Torti, F. M., Bristow, M. M., Lum, B. L., Carter, S. K., Howes, A. E., Aston, D. A., Brown, Jr, B. W., Hannigan, Jr, J. F., Meyers, F. J., Mitchell, E. P. and Billingham, M. E. (1986).Cancer Res. 46:3722–3727.
Tritton, T. R., Yee, G. and Wingard, L. B. (1983).Fed. Proc. 42:284–287.
Tritton, T. R. and Yee, G. (1982).Science 217:248–250.
Trudgill, P. W. (1985). In:Handbook of Methods for Oxygen Radical Research (R. A. Greenwald, Ed.), CRC Press, Boca Raton, FL, pp. 329–342.
Zweier, J. L. (1986).J. Biol. Chem. 259:6056–6058.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grankvist, K., Henriksson, R. Doxorubicin and epirubicin iron-induced generation of free radicalsIn vitro. A comparative study. Biosci Rep 7, 653–658 (1987). https://doi.org/10.1007/BF01127678
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01127678