Adriamycin-induced histamine release from heart tissue in vitro |
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Authors: | G Decorti Luigi Candussio Fiora Bartoli Klugmann Antonella Strohmayer Maria Pia Mucci Alessandro Mosco Luciano Baldini |
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Institution: | (1) Department of Biomedical Sciences, University of Trieste, Via L. Giorgieri 7, I-34100 Trieste, Italy Tel.: +39-40-6 76 79 49; Fax: +39-40-5 54 77, IT;(2) Department of Nuclear Medicine, Ospedale Maggiore, Trieste, Italy, IT |
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Abstract: | It has been proven that the anthracyclines induce an important, noncytotoxic histamine release from rat peritoneal mast cells.
As mast cells derived from different tissues exhibit marked heterogeneity, the effect of Adriamycin in comparison with other
antineoplastic agents was tested on fragments of the right heart auricle, which contain a great number of mast cells. In this
experimental model, Adriamycin induced a dose-dependent histamine release that was significantly limited by the antiexocytotic
drug sodium cromoglycate. The antineoplastic agents cisplatin and 5-fluorouracil, in contrast, did not provoke any comparable
histamine release. In the formulation employed in clinical settings, paclitaxel was also capable of inducing a histamine release
comparable with that of Adriamycin; the exocytotic activity, however, was also evident when the tissue fragments were treated
with Cremophor EL alone, without the addition of paclitaxel, whereas treatment of samples with paclitaxel dissolved in ethanol
did not induce any releasing action. These data thus suggest that the secretory activity should be ascribed to the solvent
Cremophor EL and not to paclitaxel. The release of histamine induced by paclitaxel in Cremophor EL/ethanol was also limited
by sodium cromoglycate. These results again indicate that histamine release from mast cells derived not only from the peritoneal
cavity but also from the cardiac tissue could play a role in the cardiotoxicity of anthracyclines and of paclitaxel in the
clinically employed formulation.
Received: 18 August 1996 / Accepted: 22 December 1996 |
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Keywords: | Adriamycin Paclitaxel Heart tissue Histamine release Cremophor EL |
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