Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy.
Adult
Animals
Anthelmintics
/ administration & dosage
Drug Monitoring
/ methods
Female
Humans
Male
Metabolome
/ drug effects
Mice, Inbred ICR
Perhexiline
/ administration & dosage
Praziquantel
/ administration & dosage
Proton Magnetic Resonance Spectroscopy
/ methods
Schistosoma mansoni
/ drug effects
Schistosomiasis mansoni
/ drug therapy
Journal
PLoS neglected tropical diseases
ISSN: 1935-2735
Titre abrégé: PLoS Negl Trop Dis
Pays: United States
ID NLM: 101291488
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
15
05
2020
accepted:
02
09
2020
revised:
22
10
2020
pubmed:
13
10
2020
medline:
9
2
2021
entrez:
12
10
2020
Statut:
epublish
Résumé
Schistosomiasis is one of the most devastating neglected tropical parasitic diseases caused by trematodes of the genus Schistosoma. Praziquantel (PZQ) is today the only drug used in humans and animals for the treatment of schistosomiasis but unfortunately it is poorly effective on larval and juvenile stages of the parasite. Therefore, it is urgent the discovery of new drug targets and compounds. We have recently showed that the anti-anginal drug perhexiline maleate (PHX) is very active on multiple developmental stages of Schistosoma mansoni in vitro. It is well known that PHX impacts the lipid metabolism in mammals, but the final target on schistosomes still remains unknown. The aim of this study was to evaluate the ability of 1H nuclear magnetic resonance (NMR) spectroscopy in revealing metabolic perturbations due to PHX treatment of S. mansoni adult male worms. The effects of PHX were compared with the ones induced by vehicle and gambogic acid, in order to detect different metabolic profiles and specificity of the PHX action. Remarkably a list of metabolites associated to PHX-treatment was identified with enrichment in several connected metabolic pathways including also the Kennedy pathway mediating the glycerophospholipid metabolism. Our study represents the first 1H-NMR metabolomic approach to characterize the response of S. mansoni to drug treatment. The obtained "metabolic fingerprint" associated to PHX treatment could represent a strategy for displaying cellular metabolic changes for any given drug and to compare compounds targeting similar or distinct biochemical pathways.
Identifiants
pubmed: 33044962
doi: 10.1371/journal.pntd.0008767
pii: PNTD-D-20-00851
pmc: PMC7580944
doi:
Substances chimiques
Anthelmintics
0
Praziquantel
6490C9U457
perhexiline maleate
K7V8Y90G0H
Perhexiline
KU65374X44
Types de publication
Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0008767Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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