Mitigating Effects of ICKF-159 (Kazoxane) on a Daunomycin-Induced Cardzomyopathy in Mice

Abstract

In an attempt to induce in mice the cardiomyopathy associated with daunomycin treatment and to ameliorate this disorder by a protective pretreatment with ICRF-159 (razoxane), young male BDF 1 mice were injected with daunomycin, 6 mg/kg, in multiple doses. A second group of mice were pretreated by injection with razoxane, 200 mg/kg, 24 hours before each daunomycin administration. Within three weeks of the third daunomycin injection one half of the unprotected mice were moribund and were sacrificed. Mice pretreated with razoxane survived the length of the experiment without exhibiting any disabilities. Myocardial tissue of all mice was processed for light and electron microscopic examination. The myocardial ultrastructure of daunomycin-toxic mice showed foci of incipient changes, characterized by sarcoplasmic translucency, vacuolation of membrane-limited components, degeneration of mitochondria and lysosomal aggregates. Evaluation of mice pretreated with razoxane either failed to reveal ultrastructural alterations or demonstrated only minimal changes in the myocardium.