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- W207173677 abstract "Dichloroacetate (DCA) is a product of water chlorination and the metabolism of other xenobiotics to which humans are exposed. It is also an investigational drug for the treatment of diseases of mitochondrial energetics, including congenital forms of lactic acidosis. DCA derives its therapeutic value from its ability to constitutively activate the mitochondrial pyruvate dehydrogenase complex, thereby facilitating lactate removal and cellular energy production. DCA has been shown to be carcinogenic to rodents at higher doses. Although there is no evidence for carcinogenicity in humans in multiple clinical trials, studies indicate that DCA exposure could lead to hepatic and/or peripheral nerve toxicity. A number of recent developments have led to an increased understanding of the biotransformation and toxicology of DCA, including the identification of glutathione S-transferase zeta 1 (GSTZ1) as the cytosolic enzyme that biotransforms DCA to glyoxylate, and that GSTZ1 is identical to maleylacetoacetate isomerase (MAAI). Several functional single nucleotide polymorphisms (SNP) have been identified in GSTZ1. This review focuses on the relevance of theses recent findings to understanding the biotransformation and toxicogenetics of DCA." @default.
- W207173677 created "2016-06-24" @default.
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- W207173677 date "2003-01-01" @default.
- W207173677 modified "2023-10-17" @default.
- W207173677 title "Biotransformation, Toxicology and Pharmacogenomics of Dichloroacetate" @default.
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- W207173677 doi "https://doi.org/10.1007/b10453" @default.
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