[Cardiotoxic study of aclacinomycin A. Subacute cardiotoxicity of aclacinomycin A and its recovery in hamsters (author's transl)]

S Hirano, H Tone, T Sunaga
Japanese Journal of Antibiotics 1980, 33 (3): 268-80
Male golden hamsters were treated with aclacinomycin A or adrianmycin by daily intraperitoneal injections for 15 consecutive days, and then allowed to be recovered for 15 days. Dose levels of aclacinomycin A and adriamycin were 1.5, 2.0 and 3.0 mg/kg, and 0.17 and 0.5 mg/kg, respectively. General toxicity, electrocardiogram (ECG), blood biochemical analysis and light microscopic and electron microscopic examinations were studied. The two drugs produced body weight loss at a dose of 3.0 mg/kg and 0.5 mg/kg, respectively. Death occurred in hamsters treated with aclacinomycin A at the highest dose (4/6 animals). In ECG study, aclacinomycin A-treated hamsters showed reversible QRS duration prolongation and T wave flattening at a dose of 1.5 or 2.0 mg/kg. Adriamycin-treated animals at a dose of 0.5 mg/kg showed R wave amplitude elevation during dosing period, and PR interval prolongation, R wave amplitude elevation and S wave amplitude reduction during recovery period. Blood biochemical analysis demonstrated reversible elevation of lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase activities in aclacinomycin A-treated hamsters at a dose of 2.0 mg/kg, and an increase in lipoperoxide in adriamycin-treated animals at a dose of 0.5 mg/kg during dosing period. Histologically, both drugs produced separation of myofilaments, swelling of mitochondria, dilation of sarcoplasmic reticulums and decreases in glycogen and lipid particles in myocardium. But aclacinomycin A-treated hamsters rarely showed these alterations after recovery period, whereas adriamycin-treated animals showed separation and necrosis of myofilaments, fibrosis of muscle fibers and formation of myelin figure even after recovery period. These results suggested that cardiotoxicity caused by aclacinomycin A was reversible and milder than that by adriamycin.

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