Klugmann F B, Decorti G, Candussio L, Mallardi F, Grill V, Zweyer M, Baldini L
Institute of Pharmacology, University of Trieste, Italy.
Eur J Cancer Clin Oncol. 1989 Feb;25(2):361-8. doi: 10.1016/0277-5379(89)90031-x.
Epirubicin induces an important noncytotoxic release of histamine from rat peritoneal cells in vitro. This exocytotic response is inhibited by sodium cromoglycate, similarly to that elicited by the classic mast cell secretagogue, compound 48/80. Mast cells obtained from the peritoneal cavities of rats treated with epirubicin in vivo were extensively degranulated; in contrast, samples obtained from rats pretreated with sodium cromoglycate showed normal appearing mast cells. When injected i.p., immediately before the antineoplastic agent, cromolyn significantly improved the survival time and the microscopic appearance of myocardial tissues of epirubicin-treated mice. The results indicate that histamine release could play an important role in the pathogenesis of anthracycline-induced cardiotoxicity.
表柔比星在体外可诱导大鼠腹膜细胞释放组胺，且这种释放具有重要的非细胞毒性。这种胞吐反应可被色甘酸钠抑制，这与经典肥大细胞促分泌剂化合物48/80所引发的反应类似。体内经表柔比星处理的大鼠腹腔中获取的肥大细胞出现广泛脱颗粒；相反，从经色甘酸钠预处理的大鼠中获取的样本显示肥大细胞外观正常。当在抗肿瘤药物给药前立即腹腔注射时，色甘酸钠可显著延长表柔比星处理小鼠的存活时间，并改善其心肌组织的微观外观。结果表明，组胺释放可能在蒽环类药物诱导的心脏毒性发病机制中起重要作用。
