Daunomycin-induced cardiomyopathy in rats and its possible therapy with peptide preparation isolated from the heart

Abstract

A well-known consequence of treating malignant diseases with anthracycline antibiotics (AA), and the first to be noted by clinicians, is their cardiotropy, result ing in cardiomyopathy, in some cases with progressive heart failure and even a lethal ou tcome. Due to the high affinity of AA to membranes and their ability to intercalate between D N A bases, the immedia te and delayed effects of anthracycline therapy are manifested in inhibition of nucleic acid and protein synthesis, reduced activity of the mitochondrial respiratory enzymes, and disturbances of ion homeostasis . This results in an energy deficit, an overload with metabol ica l ly inactive calcium, and LPO activation in the cells, as well as impaired contractile funct ion, and enhanced diastolic rigidity of the myoca rd ium [5,7]. Bearing in mind that there are no effective means for protect ing the myoca rd ium under condi t ions of anthracycline cardiomyopathy, we proposed a peptide preparat ion f rom the heart (HP) which is known to s t imula te c a r d i o m y o c y t e repai r af ter damage caused by industrial toxins [2] and to possess an antiischemic effect [6]. In the present study we tested the possibility of correcting daunomycin-induced cardiomyopathy with the heart-derived peptide preparation.