Apoptosis in young rats with adriamycin-induced cardiomyopathy--comparison with pirarubicin, a new anthracycline derivative.
In a previous study, we demonstrated that apoptosis in rats with adriamycin (ADR)-induced cardiomyopathy occurred through a Fas-dependent pathway. Pirarubicin, a new anthracycline derivative, seems to have a lower cardiotoxicity than ADR. To investigate whether pirarubicin has a lower chronic cardiotoxicity compared with ADR, ADR or pirarubicin were injected weekly for 8 wk into young Wister rats via the tail vein. To block the Fas-Fas ligand interaction, an anti-Fas ligand antibody (FasL) was injected with ADR 7, 8, and 9 wk after first administration of ADR. In the control group, saline was injected instead of ADR. ADR significantly induced apoptosis and left ventricular dysfunction 10 wk after the first administration of ADR. Pirarubicin also induced apoptosis, however, its apoptosis was significantly (p = 0.0069) less than that induced by ADR. Fas antigen was overexpressed in the hearts of ADR and ADR+FasL groups, however, an expression of Fas antigen in the pirarubicin group was similar to the expression of Fas antigen in the control group. Thus, pirarubicin has a significantly lower chronic cardiotoxicity compared with ADR.
Koh
Eikan
E
Department of Pediatrics, Kanazawa Medical University, Kanazawa, 920-0293, Japan. p-koh@kanazawa-med.ac.jp
Ueda
Yosimichi
Y
Nakamura
Tsuneyuki
T
Kobayashi
Azusa
A
Katsuta
Shogo
S
Takahashi
Hiroaki
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis / Q000502:physiology*; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology*; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D053222:Fas Ligand Protein; D006321:Heart / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D019014:fas Receptor / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D019014:fas Receptor; D004317:Doxorubicin; C027260:pirarubicin