The Antimalarial Drug Artesunate Attenuates Cardiac Injury in A Rodent Model of Myocardial Infarction.

Details

Serval ID
serval:BIB_5694E7648F91
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Antimalarial Drug Artesunate Attenuates Cardiac Injury in A Rodent Model of Myocardial Infarction.
Journal
Shock
Author(s)
Khan A.I., Kapoor A., Chen J., Martin L., Rogazzo M., Mercier T., Decosterd L., Collino M., Thiemermann C.
ISSN
1540-0514 (Electronic)
ISSN-L
1073-2322
Publication state
Published
Issued date
06/2018
Peer-reviewed
Oui
Volume
49
Number
6
Pages
675-681
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Ischemic heart disease remains the leading cause of morbidity and mortality in the Western world. Artesunate is the WHO-recommended drug of choice for complicated malaria (with organ failure). The administration of high doses of artesunate is safe in healthy volunteers (up to 8 mg/kg i.v.) and patients with severe malaria (2.4 mg/kg i.v.). We investigated the effects of artesunate (1 mg/kg) or its active metabolite dihydroartemisinin (DHA; 0.1 mg/kg) in a model of transient myocardial ischemia/reperfusion (I/R) and evaluated the mechanism of action of the observed cardioprotective effects of artesunate and DHA. We report here for the first time that the administration of artesunate at the onset of reperfusion attenuates the myocardial injury associated with I/R. The observed beneficial effects of artesunate are associated with activation of the PI3K/Akt/ERK 1/2 (RISK) pathway, activation of endothelial nitric oxide synthase, inhibition of glycogen synthase kinase-3β, inhibition of nuclear factor kappa B, and activation of the STAT3 (SAFE) pathway. In conclusion, as artesunate has an excellent safety profile, the above data should stimulate clinical trials in patients with acute coronary syndromes.
Keywords
Animals, Antimalarials/pharmacokinetics, Antimalarials/pharmacology, Artesunate/pharmacokinetics, Artesunate/pharmacology, Disease Models, Animal, Glycogen Synthase Kinase 3 beta/metabolism, MAP Kinase Signaling System/drug effects, Male, Myocardial Infarction/drug therapy, Myocardial Infarction/metabolism, Myocardial Infarction/pathology, Myocardium/metabolism, Myocardium/pathology, Phosphatidylinositol 3-Kinases/metabolism, Proto-Oncogene Proteins c-akt/metabolism, Rats, Rats, Wistar, STAT3 Transcription Factor/metabolism
Pubmed
Web of science
Create date
17/05/2018 18:39
Last modification date
20/08/2019 15:10
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