Comparative study of chronic toxic effects of daunorubicin and doxorubicin in rabbits.
This study compares the chronic toxicity of two anthracyclines--daunorubicin and doxorubicin, commonly used for induction of anthracycline cardiomyopathy in the rabbit model. Such a comparative study has not been published until now. Both drugs were administered intravenously to male Chinchilla rabbits in doses at 3 mg/kg (50 mg/m2) once weekly for 10 weeks. Selected biochemical, haematological and cardiovascular parameters and body weights were regularly monitored; additionally, a histological evaluation of heart, kidney and liver was performed at the end of the experiment. In the daunorubicin group, there were marked signs of the progressive development of heart failure, like the significant increases of the pre-ejection period/left ventricular ejection time index values (up to 134%)--and histological changes within the myocardium were also observed. On the other hand, the 10-week doxorubicin administration did not cause these changes that are typical for heart injury. Haematotoxicity, manifested particularly by aplastic anaemia, was apparent in both the experimental groups. Significant body weight loss (by 45.2%) and high premature mortality (100% versus 36.4%) reflected a greater general toxicity, especially nephrotoxicity of doxorubicin in comparison with daunorubicin. Further studies are necessary to find a possible explanation for these findings.
Klimtová
Ivona
I
Department of Pharmacology and Toxicology, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Czech Republic. klimtova@faf.cuni.cz
Simůnek
Tomás
T
Mazurová
Yvona
Y
Hrdina
Radomír
R
Gersl
Vladimír
V
Adamcová
Michaela
M
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D019963:Clinical Chemistry Tests; D003630:Daunorubicin / Q000633:toxicity*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced / Q000473:pathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D036401:Toxicity Tests, Chronic; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D003630:Daunorubicin