Adriamycin-induced changes of creatine kinase activity in vivo and in cardiomyocyte culture.
Adriamycin (ADM) is an anthracycline anti-neoplastic agent, whose clinical effectiveness is limited by severe side effects, including cardiotoxicity. The toxic effects of ADM are likely to be the consequence of the generation of free radicals. This study demonstrates that ADM induces significant changes in the activity of the oxidative sensitive enzyme creatine kinase (CK) in the heart in vivo and in a cardiomyocyte culture model. The changes observed are likely to reflect the ability of ADM to damage the plasma membrane of cardiac cells and to induce the direct inactivation of CK. The role for ADM-derived free radicals is one of the possible mechanisms for the CK inactivation observed during the ADM treatment.
Department of Pharmacology, University of Kentucky, Lexington 40506-0055, USA.
S M
SM
DeAtley
M Y
MY
Aksenov
M V
MV
Aksenova
B
B
Jordan
J M
JM
Carney
D A
DA
Butterfield
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity*; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D013482:Superoxide Dismutase; D003402:Creatine Kinase