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

https://doi.org/10.1016/j.lab.2004.03.004Get rights and content

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 (CoQ10; 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 CoQ10 supplementation. After anesthesia, Sprague-Dawley rats received intravenous saline solution (control; n = 5), DCA (n = 5; 20 mg/100 g), or CoQ10 (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 CoQ10 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 CoQ10 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.

Section snippets

Animals

Fifteen male Sprague-Dawley rats weighing 400 to 500 g were used in the study. On their arrival at the laboratory, they were kept in a special room and supplied with water and food ad libitum for at least 3 days before being subjected to any handling. After the induction of anesthesia with the use ofintraperitoneal ketamine (11 mg/100 g) and xylazine (0.5 mg/100 g), we laid the animals out on a thermoregulated mattress to keep their core temperatures constant during the control phase. We

Glucose and lactate measurements

We observed increased plasma lactate levels and a significant increase in muscle glucose content at 4 hours for all animals in the control group (P < .05; Table I). No lactatemia variation was noted, but we saw a decrease in muscle lactate content (P < .05) and an increase in muscle glucose content (P < .05) in the animals assigned to the DCA group. We noted only increased plasma lactate levels in the animals in the CoQ10 group.

Glycolysis activity

At a 37°C measurement temperature, we noted an overall increase in

Discussion

As observed in previous studies, animals demonstrate significant increases in glycolytic flux within 4 hours of the induction of sepsis induction3, 7; this effect is less pronounced in the hyperthermia range than in the hypothermia range (Table III). The absence of glycolytic flux increase in response to a temperature increase in septic control animals within the hyperthermia range (decreased Q10) as depicted in this experiment, associated with decreased oxidative phosphorylation as already

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