Abstract
The effects of dichloroacetate (DCA) and trichloroacetate (TCA) administered in drinking water were studied. At high concentrations of either compound, weight loss, or failure to gain weight, was observed. Food consumption was also decreased; both effects were attributed to decreased water consumption. Renal phosphate-dependent glutaminase activity was increased at the highest concentration, and urinary ammonia was also increased. These changes indicated renal adaptation to an acid load. DCA, in pharmacological doses, impairs glucoenogenesis from lactate in part by decreasing lactate availability. Similar tendencies were observed in the present studies; however, female rats showed a biphasic response. At lower DCA concentrations, tissue lactate and plasma glucose concentrations were increased, whereas at higher concentrations of DCA, the expected decreases were observed.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Crabb D. W., Yount E. A., Harris R. A. The metabolic effects of dichloroacetate. Metabolism. 1981 Oct;30(10):1024–1039. doi: 10.1016/0026-0495(81)90105-0. [DOI] [PubMed] [Google Scholar]
- Curthoys N. P., Kuhlenschmidt T. Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase. J Biol Chem. 1975 Mar 25;250(6):2099–2105. [PubMed] [Google Scholar]
- Curthoys N. P., Lowry O. H. The distribution of glutaminase isoenzymes in the various structures of the nephron in normal, acidotic, and alkalotic rat kidney. J Biol Chem. 1973 Jan 10;248(1):162–168. [PubMed] [Google Scholar]
- Gardell S. J., Tate S. S. Modification of the acceptor binding site of gamma-glutamyl transpeptidase by the diazonium derivatives of p-aminohippurate and p-aminobenzoate. Arch Biochem Biophys. 1982 Jul;216(2):719–726. doi: 10.1016/0003-9861(82)90262-4. [DOI] [PubMed] [Google Scholar]
- Ohmori S., Ikeda M., Kira S., Ogata M. Colorimetric determination of hippuric acid in urine and liver homogenate. Anal Chem. 1977 Sep;49(11):1494–1496. doi: 10.1021/ac50019a009. [DOI] [PubMed] [Google Scholar]
- Stacpoole P. W., Moore G. W., Kornhauser D. M. Toxicity of chronic dichloroacetate. N Engl J Med. 1979 Feb 15;300(7):372–372. doi: 10.1056/NEJM197902153000726. [DOI] [PubMed] [Google Scholar]
- Welbourne T. C., Dass P. D. Role of hippurate in acidosis induced adaptation in renal gamma-glutamyltransferase. Life Sci. 1981 Jul 20;29(3):253–258. doi: 10.1016/0024-3205(81)90241-1. [DOI] [PubMed] [Google Scholar]
- Yount E. A., Felten S. Y., O'Connor B. L., Peterson R. G., Powell R. S., Yum M. N., Harris R. A. Comparison of the metabolic and toxic effects of 2-chloropropionate and dichloroacetate. J Pharmacol Exp Ther. 1982 Aug;222(2):501–508. [PubMed] [Google Scholar]