Targeting liver stage malaria with metformin

Detalhes bibliográficos
Autor(a) principal: Vera, Iset
Data de Publicação: 2019
Outros Autores: Ruivo, Margarida, LEMOS ROCHA, Leonardo Filipe, Marques, Sofia, Bhatia, Sangeeta N., Mota, Maria M., Mancio-Silva, Liliana
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/50330
Resumo: Copyright: © 2019, American Society for Clinical Investigation
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spelling Targeting liver stage malaria with metforminDrug therapyInfectious diseaseMalariaMicrobiologyParasitologyCopyright: © 2019, American Society for Clinical InvestigationDespite an unprecedented 2 decades of success, the combat against malaria - the mosquito-transmitted disease caused by Plasmodium parasites - is no longer progressing. Efforts toward eradication are threatened by the lack of an effective vaccine and a rise in antiparasite drug resistance. Alternative approaches are urgently needed. Repurposing of available, approved drugs with distinct modes of action are being considered as viable and immediate adjuncts to standard antimicrobial treatment. Such strategies may be well suited to the obligatory and clinically silent first phase of Plasmodium infection, where massive parasite replication occurs within hepatocytes in the liver. Here, we report that the widely used antidiabetic drug, metformin, impairs parasite liver stage development of both rodent-infecting Plasmodium berghei and human-infecting P. falciparum parasites. Prophylactic treatment with metformin curtails parasite intracellular growth in vitro. An additional effect was observed in mice with a decrease in the numbers of infected hepatocytes. Moreover, metformin provided in combination with conventional liver- or blood-acting antimalarial drugs further reduced the total burden of P. berghei infection and substantially lessened disease severity in mice. Together, our findings indicate that repurposing of metformin in a prophylactic regimen could be considered for malaria chemoprevention.This work was supported by Fundação para a Ciência e Tecnologia (Portugal) PTDC/SAU-MET/118199/2010 to LMS and European Research Council Proof of Concept Grant to MMM (ERC-2015-PoC-DL3–713691-REUSE4MALARIA).American Society for Clinical InvestigationRepositório da Universidade de LisboaVera, IsetRuivo, MargaridaLEMOS ROCHA, Leonardo FilipeMarques, SofiaBhatia, Sangeeta N.Mota, Maria M.Mancio-Silva, Liliana2021-12-10T14:03:22Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50330engJCI Insight. 2019 Dec 19;4(24):e12744110.1172/jci.insight.1274412379-3708info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:54:27Zoai:repositorio.ul.pt:10451/50330Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:48.689871Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Targeting liver stage malaria with metformin
title Targeting liver stage malaria with metformin
spellingShingle Targeting liver stage malaria with metformin
Vera, Iset
Drug therapy
Infectious disease
Malaria
Microbiology
Parasitology
title_short Targeting liver stage malaria with metformin
title_full Targeting liver stage malaria with metformin
title_fullStr Targeting liver stage malaria with metformin
title_full_unstemmed Targeting liver stage malaria with metformin
title_sort Targeting liver stage malaria with metformin
author Vera, Iset
author_facet Vera, Iset
Ruivo, Margarida
LEMOS ROCHA, Leonardo Filipe
Marques, Sofia
Bhatia, Sangeeta N.
Mota, Maria M.
Mancio-Silva, Liliana
author_role author
author2 Ruivo, Margarida
LEMOS ROCHA, Leonardo Filipe
Marques, Sofia
Bhatia, Sangeeta N.
Mota, Maria M.
Mancio-Silva, Liliana
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Vera, Iset
Ruivo, Margarida
LEMOS ROCHA, Leonardo Filipe
Marques, Sofia
Bhatia, Sangeeta N.
Mota, Maria M.
Mancio-Silva, Liliana
dc.subject.por.fl_str_mv Drug therapy
Infectious disease
Malaria
Microbiology
Parasitology
topic Drug therapy
Infectious disease
Malaria
Microbiology
Parasitology
description Copyright: © 2019, American Society for Clinical Investigation
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
2021-12-10T14:03:22Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/50330
url http://hdl.handle.net/10451/50330
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv JCI Insight. 2019 Dec 19;4(24):e127441
10.1172/jci.insight.127441
2379-3708
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Clinical Investigation
publisher.none.fl_str_mv American Society for Clinical Investigation
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
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collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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