Dichloroacetate Prevents Hypoxic Lactic Acidosis in Rats|
Gahutu, Jean Bosco
Lactic acidosis has different causes, including hypoxia. It is notably treated with dichloroacetate, which stimulates the activity of the pyruvate dehydrogenase enzyme complex in the mitochondrial inner membrane. However, there has been controversy over its efficiency in hypoxic lactic acidosis, particularly in the cerebral tissue and the cerebrospinal fluid. Assess the efficiency of dichloroacetate in the prevention of hypoxia-induced lactic acidosis.We used adult rats, 3 months old, with a weight of 250-300 grams. Anesthesia was achieved by intraperitoneal injection of pentobarbital (Nembutal®), at the dose of 50 mg/kg. For the induction of hypoxia, the rats were given to inspire a gas mixture containing 11% O2 during 45 minutes. There were 20 rats in the dichloroacetate group and 20 in the control group. The dichloroacetate group rats were given dichloroacetate 300 mg/kg in slow IV injection before the induction of hypoxia. We measured lactate concentration in the blood and in the cerebrospinal fluid before the induction of hypoxia and at the end of 45 minutes of hypoxia, by spectrophotometry based on enzymatic principle. In normoxia, the lactate concentration was 1.84 ± 0.11 mmol/L in the blood and 2.00 ± 0.15 mmol/L in the cerebrospinal fluid. After 45 minutes of hypoxia, lactate concentration was 2.15 ± 0.36 mmol/L in the blood and 2.87 ± 0.16 mmol/L in the cerebrospinal fluid for the dichloroacetate group versus respectively 5.28 ± 0.91 mmol/L and 5.33 ± 0.58 mmol/L for the control group, p < 0.01.. The study shows that Dichloroacetate is efficient for the prevention of hypoxic lactic acidosis.
hypoxia, lactic acidosis, prevention, dichloroacetate.