Cardiotoxicity of a new anthracycline derivative (SM-5887) following intravenous administration to rabbits: comparative study with doxorubicin.
The degree of cardiotoxicity of SM-5887 compared with that of doxorubicin was investigated in rabbits. Two experimental groups were administered high and low doses of SM-5887, respectively. One group was administered doxorubicin and another group was administered the vehicle only were prepared as positive and negative controls, respectively. Drugs were intravenously administered 3 times a week for 8 weeks. At terminus, electrocardiograms were recorded under anesthesia. The blood was collected for haematology and blood biochemistry analyses. Myocardial tissue damage was evaluated using light and electron microscopy. In the electrocardiogram study, prolongation of QTc interval and ST-T change were observed in rabbits administered SM-5887 and doxorubicin. Morphological studies showed that myocardial tissue damage in animals administered SM-5887 was comparable to that in the negative controls, and less than that observed in the positive controls. The general toxicological investigations uniformly indicated lower toxicity in the SM-5887 group than in the doxorubicin group at equivalent dosages. In total, considering the results of antitumor efficacy studies comparing SM-5887 with doxorubicin, these results indicate that the cardiotoxicity of SM-5887 is very slight, and that the general toxicity of SM-5887 is lower than that of doxorubicin.
Suzuki
T
T
Department of Laboratory Sciences, Gunma University School of Health Sciences, Japan.
Minamide
S
S
Iwasaki
T
T
Yamamoto
H
H
Kanda
H
H
D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage / Q000633:toxicity; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000473:pathology* / Q000648:ultrastructure; D011817:Rabbits
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; C055866:amrubicin