Dichloroacetate (DCA) reduces brain lactate but increases brain glutamine in experimental cerebral malaria: a¹H-NMR study

Abstract

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.

Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S-Nitrosylation

“…SNO-pdhb enhances enzyme activity. The pyruvate dehydrogenase activator DCA has been used against CM and observed to reduce metabolic acidosis in the brain and reduce mortality. , When cells are stimulated by factors, ER stress occurs . ER morphology and function balance was destroyed.…”

Metabolic Complications of Severe Malaria

“…A large study of Ghanaian children with malaria associated hyperlactataemia (n=124) showed no pharmacokinetic interaction between quinine and DCA and no unexpected adverse events with DCA when administered as a single 10-min infusion of 50 ml/kg body weight . DCA has been shown to improve outcome in a P. berghei infected rodent model of malaria and magnetic resonance imaging studies in P. berghei infected mice showed lower brain lactate levels in animals that received DCA (Rae et al 2000).…”

Severe Malaria: Metabolic Complications

“…A large study of Ghanaian children with malaria associated lactic acidosis (n=124) showed no pharmacokinetic interaction between quinine and DCA [68] and no unexpected adverse events with DCA. DCA improves outcome in a P. berghei-infected rodent model of malaria [106] and MRI studies on P. berghei infected mice show DCA lowers brain lactate levels [107]. most sensitive to the effects of hypoglycaemia.…”