J Proteome Res 2019 May 11;18(5):1970-1993. Epub 2019 Apr 11.
School of Pharmacy , Ningxia Medical University , Yinchuan 750004 , China.
Artemisinin resistance has inevitably emerged in several malaria-endemic areas and led to an incremental clinical failure rate for artemisinin-based combination therapy (ACT), which is strongly recommended by the World Health Organization (WHO). Genetically resilient malaria parasites have evolved antimalarial drug-evasion mechanisms; meanwhile, the metabolic cross-talk between the malaria parasites and the host is of significance during the invasion. The intention of this work, therefore, is to propose a feasible method to discover the systematic metabolic phenotypes of mice invaded with artemisinin-sensitive or -resistant Plasmodium berghei K173 when compared with healthy mice. Biological samples, including plasma, liver, spleen, and kidney, of mice collected after euthanasia at day 7 were subjected to H nuclear magnetic resonance spectroscopy. Multivariable data analysis was utilized to estimate the metabolic characteristics of these samples from uninfected and infected mice. In contrast with healthy mice, both sensitive and resistant malaria-parasite-infected models displayed distinct metabolic profiles. Parasite invasion significantly changed the glycolysis, Kreb's cycle, and amino acid metabolism in plasma and tissues. Decreased N, N-dimethylglycine and glycine levels in plasma from the artemisinin-sensitive P. berghei-infected group and increased lactate, lipid, and aspartate in the artemisinin-resistant P. berghei-infected group were observed, respectively. In the liver, the artemisinin-sensitive group up-regulated the glutamate level and down-regulated glutamine. Artemisinin-resistant parasite exposure decreased ethanol and allantoin levels. The levels of myo-inositol and valine in the spleen were increased due to artemisinin-sensitive P. berghei infection, together with decreased trimethylamine N-oxide, phosphocholine, β-glucose, and acetoacetic acid. In the artemisinin-resistant group, the spleen showed a remarkably increased phosphocholine content along with decreased dimethylglycine and arginine levels. In the kidney, artemisinin-sensitive P. berghei K173 caused increased lysine, glutamate, creatine, and 2-hydroxybutyrate as well as decreased ethanol. Artemisinin-resistant P. berghei led to low glycerophosphorylcholine and high acetate, betaine, and hypoxanthine. Mutual and specific altered metabolites and, accordingly, metabolic pathways induced by the infection of artemisinin-sensitive or -resistant P. berghei were therefore screened out. This should be considered a preliminary study to establish a direct relationship with the host metabolic background and artemisinin resistance.
We have submitted your request - we will update you on status within the next 48 hours.
Sign up for further access to Scientific Publications and Authors!
What are PubFacts Points?
PubFacts points are rewards to PubFacts members, which allow you to better promote your profile and articles throughout PubFacts.com
How do I earn PubFacts Points?
Each member is given 50 PubFacts points upon signing up. You can earn additional points by completing 100% of your profile, creating and participating in discussions, and sharing other members research.
What can I do with PubFacts Points?
Currently, you can use PubFacts Points to promote and increase readership of your articles.