The effects of dichloroacetate on lactate accumulation and endurance in an exercising rat model.
Severe lactic acidosis usually accompanies intense endurance exercise. It has been postulated that glycogen depletion working in concert with elevated muscle and plasma lactate levels lead to a concomitant reduction in pH. Their cumulative effect during prolonged physical exertion now leads to muscular fatigue and eventually limit endurance capacity. Therefore in the present study, dichloroacetate (DCA), a compound which enhances the rate of pyruvate oxidation thus reducing lactate formation, has been evaluated in a validated rat model of sub-maximal exercise performance. Male rats (350 g) were divided into two groups (control-saline, i.v. and DCA 5 mg/kg, i.v.) and were exercised to exhaustion in a chamber (26 degrees C) on a treadmill (11 m/min, 6 degrees incline). When compared to controls, the DCA-treated rats had longer run times (169 vs 101 min) and a decreased heating rate (0.020 vs 0.029 degrees C/min). In addition, DCA attenuated the increase in plasma lactate (28 vs 40 mg/dl) and significantly reduced both the rate and absolute amount of depletion of muscle glycogen stores. These results suggest that the activation of pyruvate dehydrogenase activity by DCA resulted in a reduction in the rate of glycogenolysis in addition to decreasing lactate accumulation by presumably limiting the availability of pyruvate for conversion to lactate, therefore increasing muscle carbohydrate oxidation via the TCA cycle. Thus DCA effected a significant delay in muscle fatigue.
Durkot
M J
MJ
U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts, USA.
De Garavilla
L
L
Caretti
D
D
Francesconi
R
R
D000140:Acidosis, Lactic / Q000378:metabolism; D000818:Animals; D001833:Body Temperature Regulation; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006003:Glycogen / Q000378:metabolism; D007773:Lactates / Q000097:blood* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018763:Muscle Fatigue / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D010807:Physical Endurance / Q000187:drug effects*; D005082:Physical Exertion / Q000187:drug effects*; D011768:Pyruvate Dehydrogenase Complex / Q000187:drug effects; D011773:Pyruvates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012420:Running; D013997:Time Factors
D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D006003:Glycogen; D003999:Dichloroacetic Acid