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The effects of dichloroacetate (DCA) on the activity of the pyruvate dehydrogenase (PDH) complex and associated changes in the lactate and glucose levels in rat brain were investigated in vivo. The average activities of the active form of the PDH complex in the brain, liver and muscle of starved rats were respectively 0.40 +/- 0.04, 0.07 +/- 0.04, and 0.17 +/- 0.11 mumol/min/g tissue, and amounted to 21, 11, and 16% of the total activity of the complex. Intraperitoneal injection of DCA (125 mg/kg) increased the percentage of the active form of the PDH complex in the brain, liver, and muscle to 107, 40, and 84%, respectively. DCA significantly lowered the lactate and glucose concentrations of the brain and blood. A lower dose of DCA (12.5 mg/kg) also caused significant increase in activity of the PDH complex in the brain, but did not significantly change the lactate or glucose concentration of the brain. These results suggest that DCA crosses the blood-brain barrier reasonably well.
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