Effects of dichloroacetate and ubiquinone infusions on glycolysis activity and thermal sensitivity during sepsis.
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.
L'Her
Erwan
E
Reánimation et Urgences Médicales, Centre Hospitalier Universitaire de la Cavale Blanche, Brest, France. erwan@lher.net
Sebert
Philippe
P
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D003067:Coenzymes; D003999:Dichloroacetic Acid / Q000008:administration & dosage*; D014450:Electron Transport Complex III / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000097:blood / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism / Q000503:physiopathology*; D014451:Ubiquinone / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D003067:Coenzymes; D011768:Pyruvate Dehydrogenase Complex; D014451:Ubiquinone; D019344:Lactic Acid; D003999:Dichloroacetic Acid; D014450:Electron Transport Complex III; C024989:coenzyme Q10; D005947:Glucose