Mechanisms of artemether toxicity on single cardiomyocytes and protective effect of nanoencapsulation.
Action potential prolongation
CamKII phosphorylation
enhanced Na+/Ca2+ exchange
pro-arrhythmogenic risks
spontaneous Ca2+ waves
Journal
British journal of pharmacology
ISSN: 1476-5381
Titre abrégé: Br J Pharmacol
Pays: England
ID NLM: 7502536
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
25
04
2019
revised:
11
06
2020
accepted:
15
06
2020
pubmed:
2
7
2020
medline:
22
6
2021
entrez:
2
7
2020
Statut:
ppublish
Résumé
The artemisinin derivative, artemether, has antimalarial activity with potential neurotoxic and cardiotoxic effects. Artemether in nanocapsules (NC-ATM) is more efficient than free artemether for reducing parasitaemia and increasing survival of Plasmodium berghei-infected mice. NCs also prevent prolongation of the QT interval of the ECG. Here, we assessed cellular cardiotoxicity of artemether and how this toxicity was prevented by nanoencapsulation. Mice were treated with NC-ATM orally (120 mg·kg Artemether prolonged action potentials (AP) upon acute exposure (at 0.1, 1, and 10 μM) of cardiomyocytes from untreated mice or after in vivo treatment. This prolongation was unrelated to blockade of K Artemether induced NCX-dependent AP lengthening (explaining QTc prolongation) and disrupted Ca
Sections du résumé
BACKGROUND AND PURPOSE
The artemisinin derivative, artemether, has antimalarial activity with potential neurotoxic and cardiotoxic effects. Artemether in nanocapsules (NC-ATM) is more efficient than free artemether for reducing parasitaemia and increasing survival of Plasmodium berghei-infected mice. NCs also prevent prolongation of the QT interval of the ECG. Here, we assessed cellular cardiotoxicity of artemether and how this toxicity was prevented by nanoencapsulation.
EXPERIMENTAL APPROACH
Mice were treated with NC-ATM orally (120 mg·kg
KEY RESULTS
Artemether prolonged action potentials (AP) upon acute exposure (at 0.1, 1, and 10 μM) of cardiomyocytes from untreated mice or after in vivo treatment. This prolongation was unrelated to blockade of K
CONCLUSION AND IMPLICATIONS
Artemether induced NCX-dependent AP lengthening (explaining QTc prolongation) and disrupted Ca
Identifiants
pubmed: 32608017
doi: 10.1111/bph.15186
pmc: PMC7484510
doi:
Substances chimiques
Sodium-Calcium Exchanger
0
Artemether
C7D6T3H22J
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4448-4463Subventions
Organisme : Coordenação de Aperfeiçoamento do Pessoal de Nível Superior
Organisme : Ministère de l'Europe et des Affaires étrangères
Organisme : Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
ID : 13 and Me 978/13
Organisme : Ministère de l'Enseignement supérieur, de la Recherche et de l'Innovation
ID : Me 978/20
Organisme : Conselho Nacional de Desenvolvimento Científico e Tecnológico
ID : 310463/2015-7
Organisme : National Institute of Science and Technology of Pharmaceutical Nanotechnology
ID : 465687/2014-8
Organisme : Minas Gerais Research Foundation
ID : APQ-02576-18
Organisme : NANOBIOMG Network-Minas Gerais
ID : RED-00007-14
Organisme : FAPEMIG
ID : 00432-13
Organisme : FAPEMIG
ID : CDS-PPM-00481-13
Informations de copyright
© 2020 The British Pharmacological Society.
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