Adriamycin-induced histamine release from heart tissue in vitro.

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.