Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes.
Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to treat cancer patients. However, the usefulness of this drug is presently limited by the development of a dose-dependent cardiotoxicity. A current hypothesis for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorodihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if reactive oxygen species (ROS) are present, to investigate the ability of ADM to generate reactive oxygen species and the potential protective effect of antioxidants in a cultured cardiomyocyte model. All three of the antioxidants (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicylic acid (5-ASA)) tested in our ADM-treated myocytes provided protection against the oxidative stress induced by the drug. These findings suggest that antioxidants modulate ADM-induced oxidative stress, and they are discussed in terms of a possible therapeutic strategy in the prevention of cardiotoxicity resulting from ADM administration.
DeAtley
S M
SM
Department of Pharmacology, University of Kentucky, Lexington 40506, USA.
Aksenov
M Y
MY
Aksenova
M V
MV
Harris
B
B
Hadley
R
R
Cole Harper
P
P
Carney
J M
JM
Butterfield
D A
DA
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D003497:Cyclic N-Oxides; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects*; D005452:Fluoresceins; D006321:Heart / Q000187:drug effects*; D019804:Mesalamine / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology; D009589:Nitrogen Oxides / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002839:Chromans; D003497:Cyclic N-Oxides; D005452:Fluoresceins; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; C065013:2',7'-dichlorodihydrofluorescein; C029217:phenyl-N-tert-butylnitrone; D019804:Mesalamine; D004317:Doxorubicin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid