ArticleThe Journal of infectious diseases2016
Decreased Rate of Plasma Arginine Appearance in Murine Malaria May Explain Hypoargininemia in Children With Cerebral Malaria.
Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Application of Multiplatform Mass Spectrometry to the Study ofInternational journal of molecular sciences · 2025Article
- A shared inflammatory signature across severe malaria syndromes manifested by transcriptomic, proteomic and metabolomic analyses.Nature communications · 2025Article
- Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions.Circulation · 2025Article
- Impact on parasitemia, survival time and pro-inflammatory immune response in mice infected withFrontiers in pharmacology · 2024Article
- Diagnosis of cerebral malaria: Tools to reduceFrontiers in cellular and infection microbiology · 2023Review
- Oxidative Stress in Malaria: Potential Benefits of Antioxidant Therapy.International journal of molecular sciences · 2022Review
- Article
- Dexamethasone increased the survival rate in Plasmodium berghei-infected mice.Scientific reports · 2021Article
- Insights into malaria pathogenesis gained from host metabolomics.PLoS pathogens · 2020Article
- L-arginine supplementation and thromboxane synthase inhibition increases cerebral blood flow in experimental cerebral malaria.Scientific reports · 2019Article
- Perspective: L-arginine and L-citrulline Supplementation in Pregnancy: A Potential Strategy to Improve Birth Outcomes in Low-Resource Settings.Advances in nutrition (Bethesda, Md.) · 2019Review
- Distinct amino acid and lipid perturbations characterize acute versus chronic malaria.JCI insight · 2019Article
- Amino acid derangements in adults with severe falciparum malaria.Scientific reports · 2019Article
- Kinetic and Cross-Sectional Studies on the Genesis of Hypoargininemia in Severe PediatricInfection and immunity · 2019Observational
- Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak.PloS one · 2019Article
- Interplay between Plasmodium falciparum haemozoin and L-arginine: implication for nitric oxide production.Malaria journal · 2018Article
- Reversal of cerebrovascular constriction in experimental cerebral malaria by L-arginine.Scientific reports · 2018Article
- Malaria in pregnancy alters l-arginine bioavailability and placental vascular development.Science translational medicine · 2018Article
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundPlasmodium infection depletes arginine, the substrate for nitric oxide synthesis, and impairs endothelium-dependent vasodilation. Increased conversion of arginine to ornithine by parasites or host arginase is a proposed mechanism of arginine depletion.
methodsWe used high-performance liquid chromatography to measure plasma arginine, ornithine, and citrulline levels in Malawian children with cerebral malaria and in mice infected with Plasmodium berghei ANKA with or without the arginase gene. Heavy isotope-labeled tracers measured by quadrupole time-of-flight liquid chromatography-mass spectrometry were used to quantify the in vivo rate of appearance and interconversion of plasma arginine, ornithine, and citrulline in infected mice.
resultsChildren with cerebral malaria and P. berghei-infected mice demonstrated depletion of plasma arginine, ornithine, and citrulline. Knock out of Plasmodium arginase did not alter arginine depletion in infected mice. Metabolic tracer analysis demonstrated that plasma arginase flux was unchanged by P. berghei infection. Instead, infected mice exhibited decreased rates of plasma arginine, ornithine, and citrulline appearance and decreased conversion of plasma citrulline to arginine. Notably, plasma arginine use by nitric oxide synthase was decreased in infected mice.
conclusionsSimultaneous arginine and ornithine depletion in malaria parasite-infected children cannot be fully explained by plasma arginase activity. Our mouse model studies suggest that plasma arginine depletion is driven primarily by a decreased rate of appearance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.