Toxicologic screening of daunorubicin (NSC-82151), adriamycin (NSC-123127), and their derivatives in rats.
The cardiotoxicity of seven anthracycline antibiotics was evaluated in small groups of rats treated with repeated intraperitoneal injections. The electrocardiogram showed a widening of the QRS complex often with the appearance of a distinct S-wave trough and occasionally with an increase or flattening of the T wave. Ventricular extrasystoles, intraventricular block, bradycardia, and heart failure developed either during treatment or after discontinuation of therapy. Based on the cumulative dose required to induce significant electrocardiographic changes, the compounds were ranked in the following order of decreasing cardiotoxicity: adriamycin, daunorubicin, NSC-149584, rubidazone, NSC-143496, daunomycin-semicarbazone, and NSC-118714. For three of these compounds used in humans (adriamycin, daunorubicin, and rubidazone) the rat screening results are in good agreement with the clinically observed cardiotoxicity.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D001835:Body Weight; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000633:toxicity*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000633:toxicity*; D004562:Electrocardiography; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006400:Hematocrit; D006452:Hemoglobinometry; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003630:Daunorubicin