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

ABSTRACT: There 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

SUBMITTER: Vincent IM 

PROVIDER: S-EPMC3940234 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature