Summary
Human neutrophils exposed to 10-4M doxorubicin and the derivatives epirubicin and thepirubicin revealed a different intracellular penetration and distribution pattern as demonstrated by fluorescence microscopy and fluorimetric determination of drug intracellular concentration. While doxorubicin was found to be a potent inducer of superoxide generation from resting cells, epirubicin exibited less superoxideinducing power. Thepirubicin on the contrary did not show any superoxide-inducing effect. Moreover the anthracyclines tested all inhibited the phorbol esterstimulated chemiluminescent response to the same extent, which suggested a common target for the drug action. Anthracycline-stimulated superoxide production seems to correlate with the cardiotoxic effects. The most cardiotoxic drug, doxorubicin, is the most potent inducer of superoxide generation, while epirubicin, which is less cardiotoxic, has a relatively limited effect on superoxide production. Thepirubicin which has been shown not to induce delayed cardiomyopathy has no effect on superoxide release from the cells.
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Schinetti, M.L., Rossini, D. & Bertelli, A. Interaction of anthracycline antibiotics with human neutrophils: superoxide production, free radical formation and intracellular penetration. J Cancer Res Clin Oncol 113, 15–19 (1987). https://doi.org/10.1007/BF00389961
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DOI: https://doi.org/10.1007/BF00389961