Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis.
Despite well-documented cardiotoxic effects, doxorubicin remains a major anticancer agent. To study the role of myocardial apoptosis following doxorubicin administration, male Wistar rats were exposed to 1.25, 2.5, and 5 mg/kg of i.p. doxorubicin and terminated on days 1-7 in groups of five. Doxorubicin caused a significant (P < 0.001) and dose-dependent induction of cardiomyocyte apoptosis at 24-48 h after the injection. Repeated injections of 2.5 mg/kg given every other day resulted in peaks of apoptosis at 24 h after each injection. However, no additive effect of repeated dosing was noted. In histological samples, alterations in the cytoskeletal apparatus with focal loss of contractile elements were seen after a single injection. Myocyte necrosis was absent. Thus, acute doxorubicin-induced cardiotoxicity involves cardiomyocyte apoptosis, a potentially preventable form of myocardial tissue loss.
Arola
O J
OJ
Department of Medicine, University of Turku, Finland.
Saraste
A
A
Pulkki
K
K
Kallajoki
M
M
Parvinen
M
M
Voipio-Pulkki
L M
LM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D020287:In Situ Nick-End Labeling; D008297:Male; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004317:Doxorubicin