Clinical pharmacology and toxicology of dichloroacetate.

• DOI: 10.1289/ehp.98106s4989
• Publication Date: 2011-05-16T13:23:44Z
• Authors: P W Stacpoole; G N Henderson; Z Yan; M O James
• Keywords: Lactic acidosis; Chronic toxicity; Xenobiotic

Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and clinicians. The chemical product water chlorination the metabolism various drugs industrial chemicals. Its accumulation in groundwater at certain Superfund sites considered potential health hazard. However, concern about DCA toxicity predicated mainly on data obtained inbred rodent strains administered doses thousands times higher than those which humans are usually exposed. In these animals, chronic administration induces hepatotoxicity neoplasia. Ironically, used animal toxicology experiments very similar clinically for or acute treatment several acquired hereditary metabolic cardiovascular diseases. As medicinal, generally well tolerated stimulates activity mitochondrial pyruvate dehydrogenase enzyme complex, resulting increased oxidation glucose lactate an amelioration lactic acidosis. By this mechanism, drug may also enhance cellular energy metabolism. dehalogenated vivo monochloroacetate glyoxylate, from it can be further catabolized glycolate, glycine, oxalate, carbon dioxide. It remains determined whether important differences its exist between environmentally relevant doses.