Decorti G, Bartoli Klugmann F, Candussio L, Baldini L
Department of Biomedical Sciences, Faculty of Medicine, Trieste, Italy.
Anticancer Res. 1996 Jan-Feb;16(1):317-20.
The effect of paclitaxel and of its solvent Cremophor EL, a polyoxyethylated castor oil on histamine release in rat peritoneal mast cells has been tested. Paclitaxel dissolved in Cremophor EL/ethanol and Cremophor EL alone induced a moderate histamine release; this secretory activity is provoked by the solvent Cremophor EL but is so scanty that it seems most unlikely to be responsible of the severe hypersensitivity reactions frequently caused by this drug. Since in a number of protocols paclitaxel is used in combination with anthracyclines, and since anthracyclines are well known histamine releasing agents, the effect of the combination of these substances was also studied. Cremophor EL did not increase the exocytotic activity of adriamycin; on the contrary, the release of histamine induced by this anthracycline was significantly limited. This is an interesting observation since it has been suggested that anthracycline-induced histamine release is involved in the pathogenesis of the cardiotoxicity caused by these drugs. Low concentrations of paclitaxel in Cremophor EL and Cremophor EL alone inhibited adriamycin uptake into the granules of mast cells, a process mediated by an active transport system, recently identified with the P-170 glycoprotein pump.
已对紫杉醇及其溶剂聚氧乙烯蓖麻油（Cremophor EL）对大鼠腹膜肥大细胞组胺释放的影响进行了测试。溶解于Cremophor EL/乙醇中的紫杉醇以及单独的Cremophor EL均可诱导适度的组胺释放；这种分泌活性是由溶剂Cremophor EL引发的，但量很少，似乎极不可能是该药物频繁引起的严重过敏反应的原因。由于在许多方案中紫杉醇与蒽环类药物联合使用，且蒽环类药物是众所周知的组胺释放剂，因此也研究了这些物质联合使用的效果。Cremophor EL并未增加阿霉素的胞吐活性；相反，这种蒽环类药物诱导的组胺释放明显受到限制。这是一个有趣的观察结果，因为有人提出蒽环类药物诱导的组胺释放与这些药物引起的心脏毒性的发病机制有关。Cremophor EL中低浓度的紫杉醇以及单独的Cremophor EL均可抑制阿霉素摄取到肥大细胞颗粒中，这一过程由一种主动转运系统介导，最近已确定该系统为P - 170糖蛋白泵。
