Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.

<h4>Background</h4>Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is t...

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Autores principales: Peerut Chienwichai, Phornpimon Tipthara, Joel Tarning, Yanin Limpanont, Phiraphol Chusongsang, Yupa Chusongsang, Poom Adisakwattana, Onrapak Reamtong
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Publicado: Public Library of Science (PLoS) 2021
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spelling oai:doaj.org-article:4044177312fd485889980ffff61317fe2021-12-02T20:24:12ZMetabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.1935-27271935-273510.1371/journal.pntd.0009706https://doaj.org/article/4044177312fd485889980ffff61317fe2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pntd.0009706https://doaj.org/toc/1935-2727https://doaj.org/toc/1935-2735<h4>Background</h4>Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment.<h4>Methodology/principal findings</h4>Adult stage S. mekongi were treated with 0, 20, 40, or 100 μg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development.<h4>Conclusions/significance</h4>Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.Peerut ChienwichaiPhornpimon TiptharaJoel TarningYanin LimpanontPhiraphol ChusongsangYupa ChusongsangPoom AdisakwattanaOnrapak ReamtongPublic Library of Science (PLoS)articleArctic medicine. Tropical medicineRC955-962Public aspects of medicineRA1-1270ENPLoS Neglected Tropical Diseases, Vol 15, Iss 9, p e0009706 (2021)
institution DOAJ
collection DOAJ
language EN
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Peerut Chienwichai
Phornpimon Tipthara
Joel Tarning
Yanin Limpanont
Phiraphol Chusongsang
Yupa Chusongsang
Poom Adisakwattana
Onrapak Reamtong
Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.
description <h4>Background</h4>Mekong schistosomiasis is a parasitic disease caused by the blood-dwelling fluke Schistosoma mekongi. This disease contributes to human morbidity and mortality in the Mekong region, posing a public health threat to people in the area. Currently, praziquantel (PZQ) is the drug of choice for the treatment of Mekong schistosomiasis. However, the molecular mechanisms of PZQ action remain unclear, and Schistosoma PZQ resistance has been reported occasionally. Through this research, we aimed to use a metabolomic approach to identify the potentially altered metabolic pathways in S. mekongi associated with PZQ treatment.<h4>Methodology/principal findings</h4>Adult stage S. mekongi were treated with 0, 20, 40, or 100 μg/mL PZQ in vitro. After an hour of exposure to PZQ, schistosome metabolites were extracted and studied with mass spectrometry. The metabolomic data for the treatment groups were analyzed with the XCMS online platform and compared with data for the no treatment group. After low, medium (IC50), and high doses of PZQ, we found changes in 1,007 metabolites, of which phosphatidylserine and anandamide were the major differential metabolites by multivariate and pairwise analysis. In the pathway analysis, arachidonic acid metabolism was found to be altered following PZQ treatment, indicating that this pathway may be affected by the drug and potentially considered as a novel target for anti-schistosomiasis drug development.<h4>Conclusions/significance</h4>Our findings suggest that arachidonic acid metabolism is a possible target in the parasiticidal effects of PZQ against S. mekongi. Identifying potential targets of the effective drug PZQ provides an interesting viewpoint for the discovery and development of new agents that could enhance the prevention and treatment of schistosomiasis.
format article
author Peerut Chienwichai
Phornpimon Tipthara
Joel Tarning
Yanin Limpanont
Phiraphol Chusongsang
Yupa Chusongsang
Poom Adisakwattana
Onrapak Reamtong
author_facet Peerut Chienwichai
Phornpimon Tipthara
Joel Tarning
Yanin Limpanont
Phiraphol Chusongsang
Yupa Chusongsang
Poom Adisakwattana
Onrapak Reamtong
author_sort Peerut Chienwichai
title Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.
title_short Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.
title_full Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.
title_fullStr Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.
title_full_unstemmed Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.
title_sort metabolomics reveal alterations in arachidonic acid metabolism in schistosoma mekongi after exposure to praziquantel.
publisher Public Library of Science (PLoS)
publishDate 2021
url https://doaj.org/article/4044177312fd485889980ffff61317fe
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