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Effects of dichloroacetate and ubiquinone infusions on glycolysis activity and thermal sensitivity during sepsis.

Abstract : Energy-metabolism disturbances during sepsis are characterized by enhanced glycolytic fluxes and reduced mitochondrial respiration. However, it is not known whether these abnormalities are the result of a specific mitochondrial alteration, decreased pyruvate dehydrogenase (PDH) complex activity, depletion of ubiquinone (CoQ(10); electron donor for the mitochondrial complex III), or all 3. In this study we sought to specify metabolism disturbances in a murine model of sepsis, using either a PDH-activator infusion (dichloroacetate, DCA) or CoQ(10) supplementation. After anesthesia, Sprague-Dawley rats received intravenous saline solution (control; n = 5), DCA (n = 5; 20 mg/100 g), or CoQ(10) (n = 5; 1 mg/100 g), before the induction of sepsis. Increased plasma lactate levels and increased muscle glucose content were observed after 4 hours in the control group. In the DCA group, a decrease in the muscle content of lactate (P <.05) and an increase in muscle glucose content (P <.05) were observed at 4 hours, but no lactatemia variation was noted. In the CoQ(10) group, only increased plasma lactate levels were observed. Increased muscle glycolysis fluxes were observed after 4 hours in the control group, but to a slighter degree in both the DCA and CoQ(10) groups. Only DCA restored a normal temperature sensitivity in the hyperthermia range, but we noted no differences in survival time. In conclusion, only DCA infusion restores normal glycolysis function.
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https://hal.univ-brest.fr/hal-00750461
Contributor : François Guerrero <>
Submitted on : Friday, November 9, 2012 - 11:47:25 PM
Last modification on : Thursday, November 29, 2018 - 4:08:50 PM

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Erwan l'Her, Philippe Sebert. Effects of dichloroacetate and ubiquinone infusions on glycolysis activity and thermal sensitivity during sepsis.. Journal of Laboratory and Clinical Medicine, Elsevier, 2004, 143 (6), pp.352-7. ⟨10.1016/j.lab.2004.03.004⟩. ⟨hal-00750461⟩

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