English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/95125
Título

Untargeted metabolomic analysis of miltefosine action in Leishmania infantum reveals changes to the internal lipid metabolism

AutorVincent, Isabel M.; Weidt, Stefan; Rivas, Luis ; Burgess, Karl; Smith, Terry K.; Ouellette, M.
Palabras claveMode of action.
Mitafosine
Lehismania
Metabolomics
Fecha de publicaciónfeb-2014
EditorElsevier
CitaciónInternational Journal for Parasitology: Drugs and Drug Resistance 4: 20- 27 (2014)
ResumenThere are many theories as to the mode of action of miltefosine against Leishmania including alterations to the membrane lipid content, induction of apoptosis and modulation of macrophage responses. Here we perform untargeted metabolomics to elucidate the metabolic changes involved in miltefosine action. Over 800 metabolites were detected, 10% of which were significantly altered after 3.75. h. Many of the changes related to an increase in alkane fragment and sugar release. Fragment release is synchronised with reactive oxygen species production, but native membrane phospholipids remain intact. Signs of DNA damage were also detected as were changes to the levels of some thiols and polyamines. After 5. h of miltefosine treatment the cells showed depleted levels of most metabolites, indicating that the cells' outer membrane integrity had become compromised and internal metabolites were escaping upon cell death. In miltefosine resistant cells, the drug was not internalised and the changes to the internal metabolite levels were not seen. In contrast, cells resistant to antimony (SbIII) had similar corresponding alterations to the levels of internal metabolites as wild-type cells. A detailed knowledge of the mode of action of miltefosine will be important to inform the design of combination therapies to combat leishmaniasis, something that the research community should be prioritising in the coming years. © 2013 The Authors.
Versión del editorhttp://dx.doi.org/10.1016/j.ijpddr.2013.11.002
URIhttp://hdl.handle.net/10261/95125
DOI10.1016/j.ijpddr.2013.11.002
ISSN2211-3207
Aparece en las colecciones: (CIB) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
Int-J-Parasitol_Drugs-and-Drug-Resistance2014_Rivas_Luis.pdf1,21 MBAdobe PDFVista previa
Visualizar/Abrir
Mostrar el registro completo
 

Artículos relacionados:


NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.