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

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

  • Khan AI Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Kapoor A Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Chen J Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Martin L Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Rogazzo M Department of Drug Science and Technology, University of Turin, Turin, Italy.
  • Mercier T Clinical Pharmacology Laboratory, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Decosterd L Clinical Pharmacology Laboratory, University Hospital and University of Lausanne, Lausanne, Switzerland.
  • Collino M Department of Drug Science and Technology, University of Turin, Turin, Italy.
  • Thiemermann C Barts and the London School of Medicine and Dentistry, William Harvey Research Institute, Queen Mary University of London, London, UK.
Show more…
  • 2018-05-15
Published in:
  • Shock (Augusta, Ga.). - 2018
Animals
Antimalarials
Artesunate
Disease Models, Animal
Glycogen Synthase Kinase 3 beta
MAP Kinase Signaling System
Male
Myocardial Infarction
Myocardium
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Rats
Rats, Wistar
STAT3 Transcription Factor
English 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.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/278063
Statistics
Document views: 53 File downloads: