Edaravone, a potent free radical scavenger, prevents anthracycline-induced myocardial cell death.
BACKGROUND
It was investigated whether edaravone, a potent free radical scavenger, would protect against anthracycline-induced cardiotoxicity and prevent cardiac function deterioration.


RESULTS
Cultured neonatal rat cardiomyocytes were stimulated by daunorubicin 1 mumol/L either with or without edaravone or superoxide dismutase mimetic Mn (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP). Cell viability was estimated by measuring the amount of lactate dehydrogenase (LDH) released into the culture medium. Apoptosis was determined by a caspase-3 activity assay and a histone - DNA complex fragment assay. To investigate whether edaravone interfered with daunorubicin's anti-tumor effect, daunorubicin and edaravone were added to human leukemia K562 cells, and the surviving cells were counted. In addition, edaravone's in vivo effect was evaluated using Sprague - Dawley rats. A total of 15 mg/kg doxorubicin was injected intraperitoneally either with or without simultaneous edaravone injection. Two and 6 weeks after the final injection, left ventricular diastolic diameter and left ventricular fraction shortening were assessed echocardiographically. The LDH assay showed that edaravone significantly inhibited LDH release from cardiac myocytes (p=0.0428). The caspase-3 activity and histone - DNA complex fragment assays demonstrated that edaravone's apoptosis suppression effect was much weaker than that of MnTMPyP. The in vivo study showed that edaravone prevented doxorubicin-induced cardiac deterioration. Finally, edaravone was found to not affect daunorubicin's anticancer effect on K562 cells.


CONCLUSIONS
Edaravone protects cardiomyocytes from anthracycline-induced cardiotoxicity via an anti-necrotic rather than an anti-apoptotic effect.
Ikegami
Ei
E
Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
Fukazawa
Ryuji
R
Kanbe
Masaru
M
Watanabe
Miki
M
Abe
Masanori
M
Watanabe
Makoto
M
Kamisago
Mitsuhiro
M
Hajikano
Miharu
M
Katsube
Yasuhiro
Y
Ogawa
Shunichi
S
D000818:Animals; D018943:Anthracyclines / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003630:Daunorubicin / Q000494:pharmacology*; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
D018943:Anthracyclines; D016166:Free Radical Scavengers; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D000077553:Edaravone; D000983:Antipyrine; D003630:Daunorubicin