Plasmodium berghei Infection: Dichloroacetate Improves Survival in Rats with Lactic Acidosis

The kinetics of Plasmodium berghei infection and the development of lactic acidosis, hypoglycemia, and anemia were defined in young Wistar rats. This model of metabolic dysfunction, which is similar to that of severe human malaria, was used to test the hypothesis that dichloroacetate, a treatment fo...

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Bibliographic Details
Published in:Experimental parasitology 1995-06, Vol.80 (4), p.624-632
Main Authors: Holloway, P.A., Knox, K., Bajaj, N., Chapman, D., White, N.J., Obrien, R., Stacpoole, P.W., Krishna, S.
Format: Article
Language:English
Subjects:
Acidosis, Lactic - drug therapy
Acidosis, Lactic - etiology
Acidosis, Lactic - mortality
Anemia - etiology
Animals
Biological and medical sciences
Blood Glucose - analysis
Dichloroacetic Acid - therapeutic use
Disease Models, Animal
Drug Therapy, Combination
Experimental protozoal diseases and models
Hematocrit
Infectious diseases
Lactates - blood
Logistic Models
Malaria - complications
Malaria - drug therapy
Male
Medical sciences
Parasitemia - complications
Parasitic diseases
Plasmodium berghei
Protozoal diseases
Quinine - therapeutic use
Random Allocation
Rats
Rats, Wistar
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Summary:The kinetics of Plasmodium berghei infection and the development of lactic acidosis, hypoglycemia, and anemia were defined in young Wistar rats. This model of metabolic dysfunction, which is similar to that of severe human malaria, was used to test the hypothesis that dichloroacetate, a treatment for lactic acidosis, prolonged survival in rats receiving a single antimalarial dose of quinine (20 mg/kg). Rats with hyperlactatemia (lactate >5 mmol/liter, N = 183) were randomized to receive either dichloroacetate (100 mg/kg, N = 99) or saline ( N = 84) and were monitored for outcome (survival or death) for 50 hr. Logistic regression modeling adjusting for baseline venous lactate concentration demonstrated that dichloroacetate increases survival rates in rats with venous lactate concentrations between 5 and 8.9 mmol/liter (odds ratio > 2.2, P < 0.021). This is the first demonstration that specific intervention to treat lactic acidosis can prolong survival and suggests that dichloroacetate may be useful as adjunctive therapy in the management of lactic acidosis complicating severe falciparum malaria.
ISSN:0014-4894
1090-2449
DOI:10.1006/expr.1995.1078