Comparison of cardiotoxicity of pirarubicin, epirubicin and doxorubicin in the rat.
The authors have examined the cardiotoxic actions of pirarubicin (THP), compared with epirubicin (EPI) and doxorubicin (DXR), on the electrocardiogram (ECG) and myocardial structure in rats. The rats were treated once a week for four weeks with DXR (total dose 10 mg/kg), and then further treated (post-treated) once a week for four weeks with THP, EPI or DXR (total dose 5 and 10 mg/kg). In the ECG study, a prolongation of QaT interval (interval from the upstroke of R wave to the apex of T wave) and a flattening of T wave were observed more severely in the rats post-treated with EPI and DXR than in those treated with THP. Also, a prolongation of QRS duration was observed more prominently in those treated with DXR than with THP and EPI. Histopathologically, a vacuolization and swelling of myocardial cells and an infiltration of mononuclear cells were observed more severely in the rats post-treated with EPI and DXR than in those treated with THP. Furthermore, a meandering of myofibril was observed in those treated with EPI and DXR, but not with THP. These results suggest that the cardiotoxic actions of THP are weaker than those of EPI and DXR and that the replacement of DXR with THP leads to more successful cancer chemotherapy with less cardiotoxicity.
Hirano
S
S
Central Research Laboratory, Mercian Corporation, Fujisawa, Japan.
Wakazono
K
K
Agata
N
N
Iguchi
H
H
Tone
H
H
D000818:Animals; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D015251:Epirubicin / Q000633:toxicity*; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009210:Myofibrils / Q000187:drug effects / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
D015251:Epirubicin; D004317:Doxorubicin; C027260:pirarubicin