Dichloroacetate (DCA) reduces brain lactate but increases brain glutamine in experimental cerebral malaria: a 1H-NMR study.
Recent findings that levels of brain lactate and alanine were elevated in murine cerebral malaria led us to investigate the effect of dichloroacetate (DCA; 60 mg/kg), an activator of pyruvate dehydrogenase, on the levels of brain metabolites, and on the survival of mice infected with Plasmodium berghei ANKA which normally causes lethal cerebral malaria. DCA significantly reduced brain lactate and alanine levels when administered to infected mice, had no effect on the TCA cycle-related metabolites glutamate, GABA and aspartate and was associated with increased brain glutamine levels: 40% of mice thus treated survived the normally lethal infection.
Rae
C
C
Department of Biochemistry, University of Sydney, New South Wales, Australia.
Maitland
A
A
Bubb
W A
WA
Hunt
N H
NH
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002952:Citric Acid Cycle; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D016779:Malaria, Cerebral / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D010962:Plasmodium berghei; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007773:Lactates; D005973:Glutamine; D001224:Aspartic Acid; D005680:gamma-Aminobutyric Acid; D003999:Dichloroacetic Acid