Risk of
cardiotoxicity is the most serious drawback of the clinical usefulness of
anthracycline antineoplastic antibiotics, which however, remain among the most powerful and widely employed anticancer drugs. In this study we have used
daunorubicin-induced
cardiomyopathy in rabbits as a model to investigate possible cardioprotective effects of
pyridoxal isonicotinoyl hydrazone (PIH)-a principal representative of a novel group of aroylhydrazone
iron chelators. Three groups of animals were used: a control group (n=11; i.v. saline),
daunorubicin-treated animals (n=11; 3mg/kg, i.v.), and animals pretreated with PIH (n=9, 25 mg/kg, i.p.) 60 min before
daunorubicin administration. All substances were administered once weekly for 10 weeks. Repeated administration of
daunorubicin caused premature death in four animals and induced conspicuous histopathological changes in the myocardium, progressive and significant impairment of systolic heart function (a decrease in left ventricular dP/dt(max), ejection fraction, an increase in the pre-ejection period/left ventricular ejection time index), and a gradual increase in cardiac
troponin T plasma concentrations. On the contrary, all the PIH-treated animals have survived all
daunorubicin applications. Furthermore, in this group, the
daunorubicin-induced cardiac changes were in most functional, biochemical as well as morphological parameters less pronounced than in the group receiving
daunorubicin alone. Hence, PIH and other aroylhydrazones merit further investigation as potentially
protective agents against
anthracycline-induced
cardiotoxicity.