Chloroquine (CQ) is an important drug used therapeutically for treatment of malaria. However, due to limited number of studies on metabolic targets of chloroquine (CQ), it is difficult to attribute mechanisms underlying resistance associated with usage of this drug. The present study aimed to investigate the metabolic signatures of CQ-resistant Plasmodium falciparum (PfDd2) compared to CQ-sensitive Plasmodium falciparum (Pf3D7). Both Pf3D7 and PfDd2 were treated with CQ at 200 nM for 48 hr; thereafter, the harvested red blood cells (RBCs) and media were subjected to microscopy and high-resolution metabolomics (HRM). Glutathione, γ-L-glutamyl-L-cysteine, spermidine, inosine monophosphate, alanine, and fructose-1,6-bisphosphate were markedly altered in PfDd2 of RBC. In the media, cysteine, cysteic acid, spermidine, phenylacetaldehyde, and phenylacetic acid were significantly altered in PfDd2. These differential metabolic signatures related signaling pathways of PfDd2, such as oxidative stress pathway and glycolysis may provide evidence for understanding the resistance mechanism and pathogenesis of the CQ-resistant parasite.
|Number of pages||16|
|Journal||Journal of Toxicology and Environmental Health - Part A: Current Issues|
|Publication status||Published - 2021|
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (Grant Numbers NRF-2017R1A2B4003890, NRF-2017M3A9F1031229, and NRF-2020R1A2C2103067). The authors thank Dr. Karan Uppal and Dr. Shuzhao Li from the Emory University School of Medicine (Atlanta, GA, USA) for providing the R-package used to run the apLCMS and xMSannotator. The author declare that Prof. Eun-Taek Han provided PfDd2 and Pf3D7 strains.
© 2021 Taylor & Francis.
- high resolution metabolomics
- red blood cells
ASJC Scopus subject areas
- Health, Toxicology and Mutagenesis