Amelioration of 4′-epidoxorubicin-induced cardiotoxicity by sodium cromoglycate

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.