Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy.
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 juvenil...
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ftdoajarticles:oai:doaj.org/article:9de522a703934102aba12d64e4e2443f 2023-05-15T15:10:55+02:00 Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy. Alessandra Guidi Greta Petrella Valentina Fustaino Fulvio Saccoccia Sara Lentini Roberto Gimmelli Giulia Di Pietro Alberto Bresciani Daniel Oscar Cicero Giovina Ruberti 2020-10-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008767 https://doaj.org/article/9de522a703934102aba12d64e4e2443f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008767 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008767 https://doaj.org/article/9de522a703934102aba12d64e4e2443f PLoS Neglected Tropical Diseases, Vol 14, Iss 10, p e0008767 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008767 2022-12-31T09:21:49Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 10 e0008767 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Alessandra Guidi Greta Petrella Valentina Fustaino Fulvio Saccoccia Sara Lentini Roberto Gimmelli Giulia Di Pietro Alberto Bresciani Daniel Oscar Cicero Giovina Ruberti Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Alessandra Guidi Greta Petrella Valentina Fustaino Fulvio Saccoccia Sara Lentini Roberto Gimmelli Giulia Di Pietro Alberto Bresciani Daniel Oscar Cicero Giovina Ruberti |
author_facet |
Alessandra Guidi Greta Petrella Valentina Fustaino Fulvio Saccoccia Sara Lentini Roberto Gimmelli Giulia Di Pietro Alberto Bresciani Daniel Oscar Cicero Giovina Ruberti |
author_sort |
Alessandra Guidi |
title |
Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy. |
title_short |
Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy. |
title_full |
Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy. |
title_fullStr |
Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy. |
title_full_unstemmed |
Drug effects on metabolic profiles of Schistosoma mansoni adult male parasites detected by 1H-NMR spectroscopy. |
title_sort |
drug effects on metabolic profiles of schistosoma mansoni adult male parasites detected by 1h-nmr spectroscopy. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008767 https://doaj.org/article/9de522a703934102aba12d64e4e2443f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 10, p e0008767 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008767 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008767 https://doaj.org/article/9de522a703934102aba12d64e4e2443f |
op_doi |
https://doi.org/10.1371/journal.pntd.0008767 |
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PLOS Neglected Tropical Diseases |
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14 |
container_issue |
10 |
container_start_page |
e0008767 |
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1766341843410223104 |