A new antithrombotic agent, aspalatone, attenuated cardiotoxicity induced by doxorubicin in the mouse; possible involvement of antioxidant mechanism.
A new antithrombotic agent, aspalatone (APT; acetyl salicylic acid maltol ester), was synthesized by esterification of acetyl salicylic acid (ASP) and maltol (MAL). It was suggested that APT possessed an antioxidant effect in in vitro. To evaluate the putative antioxidant effect of APT in in vivo, we developed doxorubicin (DOX)-related cardiac damage, which might be implicated by oxidative stress. Vitamin E (Vit E) was included in the present study as an example of an antioxidant. Prolonged treatments with APT, MAL and Vit E significantly reduced the mortality in animals receiving multiple dose of DOX (3 mg/kg x 4). The potential role of APT, MAL and Vit E against DOX insult may be explained by the induction of glutathione peroxidase activity accompanied by the inhibition of lipid peroxidation. Prolonged treatments of APT, MAL and Vit E also ablated histopathological evidence of DOX cardiomyopathy. ASP challenge, however, did not affect the mortality, myocardial lesion and antioxidant deficit induced by DOX treatments. In conclusion, the protective effect of APT was equipotent to that of Vit E against DOX cardiotoxicity. The results also suggest that the antiperoxidative effect of APT plays a protective role in DOX-related cardiotoxic side effect.
Kim
C
C
Bukwang Pharmaceutical Ind., Co., Seoul, Korea.
Nam
S W
SW
Choi
D Y
DY
Choi
J H
JH
Park
E S
ES
Jhoo
W K
WK
Kim
H C
HC
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011753:Pyrones / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D005343:Fibrinolytic Agents; D011753:Pyrones; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; C008316:maltol; D004317:Doxorubicin; C091320:aspalatone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001241:Aspirin