Pharmacotoxicology of Trichloroethylene Metabolites

Summary

This project focuses on the kinetics, metabolism and human toxicology of dichloroacetate (DCA)and tyrosine catabolism. The hypothesis is that tyrosine metabolism will be greatest in subject who harbor the KRT variant for GSTz1/MAAI for which DCA exhibits a high Km.

Timeline

Start

2011-08

Primary completion

2012-01

Completion

2012-01

Publications

• Background National Toxicology Program. Toxicology Carcinogenesis Studies of Trichloroethylene (Without Epichlorohydon)(CAS No. 7.9-011-6) in F3dd/N Rats B6C3F1 Mice (Gavage Studies). Research Triangle Park, NC: US Department of Health Human Services; Technical report series No. 243; NIH Publication 9:0-1779, 1990.
• Background LARC Monogr Eval Carcinog Risks Hum 11:263-276,1979.
• Background Page NN. Assessment of trichloroethylene as an occupational carcinogen. IARC Sci Publ (1971). 1979;(25):75-9.
• Background Federal Register 40(203):49032-49045, 1975.
• Background Westrick JJ, Mello JW, Thomas RF. The groundwater supply survey. J Am Water Works 76:52, 1984.
• Background Josephson J. ES Views: Implementing Superfund. Environ Sci Technol. 1986 Jan 1;20(1):23-8. doi: 10.1021/es00143a601. No abstract available.
• Background Brown LP, Farrar DG, de Rooij CG. Health risk assessment of environmental exposure to trichloroethylene. Regul Toxicol Pharmacol. 1990 Feb;11(1):24-41. doi: 10.1016/0273-2300(90)90005-v.
• Background Steinberg AD, DeSesso JM. Have animal data been used inappropriately to estimate risks to humans from environmental trichloroethylene? Regul Toxicol Pharmacol. 1993 Oct;18(2):137-53. doi: 10.1006/rtph.1993.1049.
• Background Nelson MA, Bull RJ. Induction of strand breaks in DNA by trichloroethylene and metabolites in rat and mouse liver in vivo. Toxicol Appl Pharmacol. 1988 Jun 15;94(1):45-54. doi: 10.1016/0041-008x(88)90335-3.
• Background Larson JL, Bull RJ. Species differences in the metabolism of trichloroethylene to the carcinogenic metabolites trichloroacetate and dichloroacetate. Toxicol Appl Pharmacol. 1992 Aug;115(2):278-85. doi: 10.1016/0041-008x(92)90333-n.
• Background Henschler D. Metabolism and mutagenicity of halogenated olefins--a comparison of structure and activity. Environ Health Perspect. 1977 Dec;21:61-4. doi: 10.1289/ehp.772161.
• Background Buben JA, O'Flaherty EJ. Delineation of the role of metabolism in the hepatotoxicity of trichloroethylene and perchloroethylene: a dose-effect study. Toxicol Appl Pharmacol. 1985 Mar 30;78(1):105-22. doi: 10.1016/0041-008x(85)90310-2.
• Background Bruckner JV, Davis BD, Blancato JN. Metabolism, toxicity, and carcinogenicity of trichloroethylene. Crit Rev Toxicol. 1989;20(1):31-50. doi: 10.3109/10408448909037475.
• Background Van Duuren BL, Banerjee S. Covalent interaction of metabolites of the carcinogen trichloroethylene in rat hepatic microsomes. Cancer Res. 1976 Jul;36(7 PT 1):2419-22.
• Background Henschler D, Romen W, Elsasser HM, Reichert D, Eder E, Radwan Z. Carcinogenicity study of trichloroethylene by longterm inhalation in three animal species. Arch Toxicol. 1980 Feb;43(4):237-48. doi: 10.1007/BF00366179.
• Background Elcombe CR. Species differences in carcinogenicity and peroxisome proliferation due to trichloroethylene: a biochemical human hazard assessment. Arch Toxicol Suppl. 1985;8:6-17. doi: 10.1007/978-3-642-69928-3_2.
• Background Forkert PG, Lash LH, Nadeau V, Tardif R, Simmonds A. Metabolism and toxicity of trichloroethylene in epididymis and testis. Toxicol Appl Pharmacol. 2002 Aug 1;182(3):244-54. doi: 10.1006/taap.2002.9421.
• Background Xu H, Tanphaichitr N, Forkert PG, Anupriwan A, Weerachatyanukul W, Vincent R, Leader A, Wade MG. Exposure to trichloroethylene and its metabolites causes impairment of sperm fertilizing ability in mice. Toxicol Sci. 2004 Dec;82(2):590-7. doi: 10.1093/toxsci/kfh277. Epub 2004 Sep 16.
• Background Gilbert KM, Whitlow AB, Pumford NR. Environmental contaminant and disinfection by-product trichloroacetaldehyde stimulates T cells in vitro. Int Immunopharmacol. 2004 Jan;4(1):25-36. doi: 10.1016/j.intimp.2003.10.001.
• Background Reif JS, Burch JB, Nuckols JR, Metzger L, Ellington D, Anger WK. Neurobehavioral effects of exposure to trichloroethylene through a municipal water supply. Environ Res. 2003 Nov;93(3):248-58. doi: 10.1016/s0013-9351(03)00131-2.
• Background Guehl D, Bezard E, Dovero S, Boraud T, Bioulac B, Gross C. Trichloroethylene and parkinsonism: a human and experimental observation. Eur J Neurol. 1999 Sep;6(5):609-11. doi: 10.1046/j.1468-1331.1999.650609.x.
• Background Miller JW, Uden PC. Characterization of nonvolatile aqueous chlorination products of humic substances. Environ Sci Technol. 1983 Mar 1;17(3):150-7. doi: 10.1021/es00109a006. No abstract available.
• Background Uden PCC, Miller JW. Chlorinated acids and chloral in drinking water. J Amer Water Works Assoc 75:524-527, 1983.
• Background Mughal FH. Chlorination of drinking water and cancer: a review. J Environ Pathol Toxicol Oncol. 1992 Sep-Oct;11(5-6):287-92. No abstract available.
• Background Jolley RL. Basic issues in water chlorination: a chemical perspective. In, Water chlorination: chemistry, environmental impact and health effects. Lewis Publ, Inc. Chelsea, MI 5:19-38, 1985.
• Background Stacpoole PW. The pharmacology of dichloroacetate. Metabolism. 1989 Nov;38(11):1124-44. doi: 10.1016/0026-0495(89)90051-6.
• Background Abbas RR, Seckel CS, Kidney JK, Fisher JW. Pharmacokinetic analysis of chloral hydrate and its metabolism in B6C3F1 mice. Drug Metab Dispos. 1996 Dec;24(12):1340-6.
• Background Duncan GE, Perkins LA, Theriaque DW, Neiberger RE, Stacpoole PW. Dichloroacetate therapy attenuates the blood lactate response to submaximal exercise in patients with defects in mitochondrial energy metabolism. J Clin Endocrinol Metab. 2004 Apr;89(4):1733-8. doi: 10.1210/jc.2003-031684.
• Background Stacpoole PW, Kerr DS, Barnes C, Bunch ST, Carney PR, Fennell EM, Felitsyn NM, Gilmore RL, Greer M, Henderson GN, Hutson AD, Neiberger RE, O'Brien RG, Perkins LA, Quisling RG, Shroads AL, Shuster JJ, Silverstein JH, Theriaque DW, Valenstein E. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics. 2006 May;117(5):1519-31. doi: 10.1542/peds.2005-1226.
• Background Kaufmann P, Engelstad K, Wei Y, Jhung S, Sano MC, Shungu DC, Millar WS, Hong X, Gooch CL, Mao X, Pascual JM, Hirano M, Stacpoole PW, DiMauro S, De Vivo DC. Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology. 2006 Feb 14;66(3):324-30. doi: 10.1212/01.wnl.0000196641.05913.27.
• Background Salmon AG, Jackson RJ, Smith MT. Chloral hydrate: cancer risk assessment of a drug previously presumed safe. The Toxicologist 11:350, 1991.
• Background Liebreich O. Das Chloral hydrat, ein neues Hypnoticum und Anaestheticum, 3rd ed. Berlin: Otto Mullers Verlag, 1869.
• Background Reimche LD, Sankaran K, Hindmarsh KW, Kasian GF, Gorecki DK, Tan L. Chloral hydrate sedation in neonates and infants--clinical and pharmacologic considerations. Dev Pharmacol Ther. 1989;12(2):57-64.
• Background Hartley S, Franck LS, Lundergan F. Maintenance sedation of agitated infants in the neonatal intensive care unit with chloral hydrate: new concerns. J Perinatol. 1989 Jun;9(2):162-4. No abstract available.
• Background Krsek P, Sebronova V, Prochazka T, Maulisova A, Komarek V. Successful treatment of Ohtahara syndrome with chloral hydrate. Pediatr Neurol. 2002 Nov;27(5):388-91. doi: 10.1016/s0887-8994(02)00464-2.
• Background Greenberg SB, Faerber EN, Aspinall CL. High dose chloral hydrate sedation for children undergoing CT. J Comput Assist Tomogr. 1991 May-Jun;15(3):467-9. doi: 10.1097/00004728-199105000-00023.
• Background Nathan JE. Management of the refractory young child with chloral hydrate: dosage selection. ASDC J Dent Child. 1987 Mar-Apr;54(2):93-100.
• Background Kuhn JP. CT of the body in children. Pediatr Ann. 1986 May;15(5):367, 371-3, 376-82. doi: 10.3928/0090-4481-19860501-07.
• Background Weir MR, Segapeli JH, Tremper LJ. Sedation for pediatric procedures. Mil Med. 1986 Mar;151(3):181-4. No abstract available.
• Background Miller RR, Greenblatt DJ. Clinical effects of chloral hydrate in hospitalized medical patients. J Clin Pharmacol. 1979 Oct;19(10):669-74. doi: 10.1002/j.1552-4604.1979.tb01630.x. No abstract available.
• Background Malviya S, Voepel-Lewis T, Tait AR, Reynolds PI, Gujar SK, Gebarski SS, Petter Eldevik O. Pentobarbital vs chloral hydrate for sedation of children undergoing MRI: efficacy and recovery characteristics. Paediatr Anaesth. 2004 Jul;14(7):589-95. doi: 10.1111/j.1460-9592.2004.01243.x.
• Background James MO, Cornett R, Yan Z, Henderson GN, Stacpoole PW. Glutathione-dependent conversion to glyoxylate, a major pathway of dichloroacetate biotransformation in hepatic cytosol from humans and rats, is reduced in dichloroacetate-treated rats. Drug Metab Dispos. 1997 Nov;25(11):1223-7.
• Background Cornett R, James MO, Henderson GN, Cheung J, Shroads AL, Stacpoole PW. Inhibition of glutathione S-transferase zeta and tyrosine metabolism by dichloroacetate: a potential unifying mechanism for its altered biotransformation and toxicity. Biochem Biophys Res Commun. 1999 Sep 7;262(3):752-6. doi: 10.1006/bbrc.1999.1287.
• Background Tong Z, Board PG, Anders MW. Glutathione transferase zeta catalyses the oxygenation of the carcinogen dichloroacetic acid to glyoxylic acid. Biochem J. 1998 Apr 15;331 ( Pt 2)(Pt 2):371-4. doi: 10.1042/bj3310371.
• Background Fernandez-Canon JM, Hejna J, Reifsteck C, Olson S, Grompe M. Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase. Genomics. 1999 Jun 15;58(3):263-9. doi: 10.1006/geno.1999.5832.
• Background Blackburn AC, Coggan M, Tzeng HF, Lantum H, Polekhina G, Parker MW, Anders MW, Board PG. GSTZ1d: a new allele of glutathione transferase zeta and maleylacetoacetate isomerase. Pharmacogenetics. 2001 Nov;11(8):671-8. doi: 10.1097/00008571-200111000-00005.
• Background Blackburn AC, Tzeng HF, Anders MW, Board PG. Discovery of a functional polymorphism in human glutathione transferase zeta by expressed sequence tag database analysis. Pharmacogenetics. 2000 Feb;10(1):49-57. doi: 10.1097/00008571-200002000-00007.
• Background MARSHALL EK Jr, OWENS AH Jr. Absorption, excretion and metabolic fate of chloral hydrate and trichloroethanol. Bull Johns Hopkins Hosp. 1954 Jul;95(1):1-18. No abstract available.
• Background Jochemsen R, Breimer DD. Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles. Curr Med Res Opin. 1984;8 Suppl 4:60-79. doi: 10.1185/03007998409109545.
• Background Henderson GN, Yan Z, James MO, Davydova N, Stacpoole PW. Kinetics and metabolism of chloral hydrate in children: identification of dichloroacetate as a metabolite. Biochem Biophys Res Commun. 1997 Jun 27;235(3):695-8. doi: 10.1006/bbrc.1997.6868.
• Background Toxicological review of dichloroacetic acid (CAS No. 79-43-6). U.S. Environ. Protection Agency. Washington, DC, August, 2003.
• Background Bull RJ, Sanchez IM, Nelson MA, Larson JL, Lansing AJ. Liver tumor induction in B6C3F1 mice by dichloroacetate and trichloroacetate. Toxicology. 1990 Sep;63(3):341-59. doi: 10.1016/0300-483x(90)90195-m.
• Background Daniel FB, DeAngelo AB, Stober JA, Olson GR, Page NP. Hepatocarcinogenicity of chloral hydrate, 2-chloroacetaldehyde, and dichloroacetic acid in the male B6C3F1 mouse. Fundam Appl Toxicol. 1992 Aug;19(2):159-68. doi: 10.1016/0272-0590(92)90147-a.
• Background DeAngelo AB, Daniel FB, Stober JA, Olson GR. The carcinogenicity of dichloroacetic acid in the male B6C3F1 mouse. Fundam Appl Toxicol. 1991 Feb;16(2):337-47. doi: 10.1016/0272-0590(91)90118-n.
• Background Pereira MA, Li K, Kramer PM. Promotion by mixtures of dichloroacetic acid and trichloroacetic acid of N-methyl-N-nitrosourea-initiated cancer in the liver of female B6C3F1 mice. Cancer Lett. 1997 May 1;115(1):15-23. doi: 10.1016/s0304-3835(97)04699-5.
• Background Pereira MA, Phelps JB. Promotion by dichloroacetic acid and trichloroacetic acid of N-methyl-N-nitrosourea-initiated cancer in the liver of female B6C3F1 mice. Cancer Lett. 1996 Apr 19;102(1-2):133-41. doi: 10.1016/0304-3835(96)04156-0.
• Background DeAngelo AB, Daniel FB, Most BM, Olson GR. The carcinogenicity of dichloroacetic acid in the male Fischer 344 rat. Toxicology. 1996 Dec 18;114(3):207-21. doi: 10.1016/s0300-483x(96)03510-x.
• Background McHugh Law J, Lopez L, DeAngelo AB. Hepatotoxicity of the drinking water disinfection by-product, dichloroacetic acid, in the medaka small fish model. Toxicol Lett. 1998 Jan 16;94(1):19-27. doi: 10.1016/s0378-4274(97)00095-7.
• Background Kato-Weinstein J, Lingohr MK, Orner GA, Thrall BD, Bull RJ. Effects of dichloroacetate on glycogen metabolism in B6C3F1 mice. Toxicology. 1998 Sep 15;130(2-3):141-54. doi: 10.1016/s0300-483x(98)00106-1.
• Background Stacpoole PW, Henderson GN, Yan Z, Cornett R, James MO. Pharmacokinetics, metabolism and toxicology of dichloroacetate. Drug Metab Rev. 1998 Aug;30(3):499-539. doi: 10.3109/03602539808996323. No abstract available.
• Background DeAngelo AB, Daniel FB, McMillan L, Wernsing P, Savage RE Jr. Species and strain sensitivity to the induction of peroxisome proliferation by chloroacetic acids. Toxicol Appl Pharmacol. 1989 Nov;101(2):285-98. doi: 10.1016/0041-008x(89)90277-9.
• Background Everhart JL, Kurtz DT, McMillan JM. Dichloroacetic acid induction of peroxisome proliferation in cultured hepatocytes. J Biochem Mol Toxicol. 1998;12(6):351-9. doi: 10.1002/(sici)1099-0461(1998)12:63.0.co;2-2.
• Background Zhou YC, Waxman DJ. Activation of peroxisome proliferator-activated receptors by chlorinated hydrocarbons and endogenous steroids. Environ Health Perspect. 1998 Aug;106 Suppl 4(Suppl 4):983-8. doi: 10.1289/ehp.98106s4983.
• Background Maloney EK, Waxman DJ. trans-Activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals. Toxicol Appl Pharmacol. 1999 Dec 1;161(2):209-18. doi: 10.1006/taap.1999.8809.
• Background Sanchez IM, Bull RJ. Early induction of reparative hyperplasia in the liver of B6C3F1 mice treated with dichloroacetate and trichloroacetate. Toxicology. 1990 Oct;64(1):33-46. doi: 10.1016/0300-483x(90)90097-z.
• Background Snyder RD, Pullman J, Carter JH, Carter HW, DeAngelo AB. In vivo administration of dichloroacetic acid suppresses spontaneous apoptosis in murine hepatocytes. Cancer Res. 1995 Sep 1;55(17):3702-5.
• Background Lingohr MK, Thrall BD, Bull RJ. Effects of dichloroacetate (DCA) on serum insulin levels and insulin-controlled signaling proteins in livers of male B6C3F1 mice. Toxicol Sci. 2001 Jan;59(1):178-84. doi: 10.1093/toxsci/59.1.178.
• Background Gonzalez-Leon A, Schultz IR, Bull RJ. Species differences in the toxicokinetics of dichloroacetate and trichloroacetate in F344 rats and B6C3F1 mice after prolonged administration in drinking water. Fundam Appl Toxicol Suppl 36, Abst. 168, p. 33, 1997.
• Background Gonzalez-Leon A, Schultz IR, Xu G, Bull RJ. Pharmacokinetics and metabolism of dichloroacetate in the F344 rat after prior administration in drinking water. Toxicol Appl Pharmacol. 1997 Oct;146(2):189-95. doi: 10.1006/taap.1997.8232.
• Background Waxman DJ. P450 gene induction by structurally diverse xenochemicals: central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys. 1999 Sep 1;369(1):11-23. doi: 10.1006/abbi.1999.1351.
• Background DeMarini DM, Perry E, Shelton ML. Dichloroacetic acid and related compounds: induction of prophage in E. coli and mutagenicity and mutation spectra in Salmonella TA100. Mutagenesis. 1994 Sep;9(5):429-37. doi: 10.1093/mutage/9.5.429.
• Background Fox AW, Yang X, Murli H, Lawlor TE, Cifone MA, Reno FE. Absence of mutagenic effects of sodium dichloroacetate. Fundam Appl Toxicol. 1996 Jul;32(1):87-95. doi: 10.1006/faat.1996.0110.
• Background Fuscoe JC, Afshari AJ, George MH, DeAngelo AB, Tice RR, Salman T, Allen JW. In vivo genotoxicity of dichloroacetic acid: evaluation with the mouse peripheral blood micronucleus assay and the single cell gel assay. Environ Mol Mutagen. 1996;27(1):1-9. doi: 10.1002/(SICI)1098-2280(1996)27:13.0.CO;2-L.
• Background Giller S, Le Curieux F, Erb F, Marzin D. Comparative genotoxicity of halogenated acetic acids found in drinking water. Mutagenesis. 1997 Sep;12(5):321-8. doi: 10.1093/mutage/12.5.321.
• Background Harrington-Brock K, Doerr CL, Moore MM. Mutagenicity of three disinfection by-products: di- and trichloroacetic acid and chloral hydrate in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells. Mutat Res. 1998 Mar 30;413(3):265-76. doi: 10.1016/s1383-5718(98)00026-6.
• Background Leavitt SA, DeAngelo AB, George MH, Ross JA. Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver. Carcinogenesis. 1997 Nov;18(11):2101-6. doi: 10.1093/carcin/18.11.2101.
• Background Rapson WH, Nazar MA, Butsky VV. Mutagenicity produced by aqueous chlorination of organic compounds. Bull Environ Contam Toxicol. 1980 Apr;24(4):590-6. doi: 10.1007/BF01608160. No abstract available.
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• Background Mariash CN, Schwartz HL. Effect of dichloroacetic acid on rat hepatic messenger RNA activity profiles. Metabolism. 1986 May;35(5):452-6. doi: 10.1016/0026-0495(86)90137-x.
• Background Barton CH, Bailey E. Changes in immunoreactive malic enzyme in liver and brown adipose tissue during development of the rat. J Dev Physiol. 1987 Jun;9(3):215-24.
• Background Barak C, Reed MK, Maniscalco SP, Sherry AD, Malloy CR, Jessen ME. Effects of dichloroacetate on mechanical recovery and oxidation of physiologic substrates after ischemia and reperfusion in the isolated heart. J Cardiovasc Pharmacol. 1998 Mar;31(3):336-44. doi: 10.1097/00005344-199803000-00002.
• Background Stacpoole PW, Harwood HJ Jr, Cameron DF, Curry SH, Samuelson DA, Cornwell PE, Sauberlich HE. Chronic toxicity of dichloroacetate: possible relation to thiamine deficiency in rats. Fundam Appl Toxicol. 1990 Feb;14(2):327-37. doi: 10.1016/0272-0590(90)90212-3.
• Background Hong JY, Pan JM, Gonzalez FJ, Gelboin HV, Yang CS. The induction of a specific form of cytochrome P-450 (P-450j) by fasting. Biochem Biophys Res Commun. 1987 Feb 13;142(3):1077-83. doi: 10.1016/0006-291x(87)91525-7.
• Background Yoo JS, Park HS, Ning SM, Lee MJ, Yang CS. Effects of thiamine deficiency on hepatic cytochromes P450 and drug-metabolizing enzyme activities. Biochem Pharmacol. 1990 Feb 1;39(3):519-25. doi: 10.1016/0006-2952(90)90059-t.
• Background Yang HM, Houser WH, Davis ME. Dichloroacetic acid treatment increases hepatic CYP2E1 in male and female rats. Toxicol Appl Pharmacol. 1996 Dec;141(2):382-8. doi: 10.1006/taap.1996.0303.
• Background Thai SF, Allen JW, DeAngelo AB, George MH, Fuscoe JC. Detection of early gene expression changes by differential display in the livers of mice exposed to dichloroacetic acid. Carcinogenesis. 2001 Aug;22(8):1317-22. doi: 10.1093/carcin/22.8.1317.
• Background NTP Technical Report. Toxicology and carcinogenesis study of chloral hydrate. NIH Publication No. 03-4437, 2002.
• Background IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Chloral hydrate. World Health Organization, 2004, pp. 317-358.
• Background Davidson IW, Beliles RP. Consideration of the target organ toxicity of trichloroethylene in terms of metabolite toxicity and pharmacokinetics. Drug Metab Rev. 1991;23(5-6):493-599. doi: 10.3109/03602539109029772.
• Background Ikbal M, Tastekin A, Dogan H, Pirim I, Ors R. The assessment of genotoxic effects in lymphocyte cultures of infants treated with chloral hydrate. Mutat Res. 2004 Dec 12;564(2):159-64. doi: 10.1016/j.mrgentox.2004.08.007.
• Background Ho YS, Ma HY, Chang HY, Wei BL, Lee CC, Ho SY, Guo HR, Wu TP, Chang WH, Wang YJ. Lipid peroxidation and cell death mechanisms in rats and human cells induced by chloral hydrate. Food Chem Toxicol. 2003 May;41(5):621-9. doi: 10.1016/s0278-6915(02)00323-x.
• Background Harinath S, Sikdar SK. Trichloroethanol enhances the activity of recombinant human TREK-1 and TRAAK channels. Neuropharmacology. 2004 Apr;46(5):750-60. doi: 10.1016/j.neuropharm.2003.11.023.
• Background Fischer W, Wirkner K, Weber M, Eberts C, Koles L, Reinhardt R, Franke H, Allgaier C, Gillen C, Illes P. Characterization of P2X3, P2Y1 and P2Y4 receptors in cultured HEK293-hP2X3 cells and their inhibition by ethanol and trichloroethanol. J Neurochem. 2003 May;85(3):779-90. doi: 10.1046/j.1471-4159.2003.01716.x.
• Background Sabeti J, Gerhardt GA, Zahniser NR. Chloral hydrate and ethanol, but not urethane, alter the clearance of exogenous dopamine recorded by chronoamperometry in striatum of unrestrained rats. Neurosci Lett. 2003 May 29;343(1):9-12. doi: 10.1016/s0304-3940(03)00301-x.
• Background Akundi RS, Macho A, Munoz E, Lieb K, Bringmann G, Clement HW, Hull M, Fiebich BL. 1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline-induced apoptosis in the human neuroblastoma cell line SK-N-SH. J Neurochem. 2004 Oct;91(2):263-73. doi: 10.1111/j.1471-4159.2004.02710.x.
• Background Templin MV, Parker JC, Bull RJ. Relative formation of dichloroacetate and trichloroacetate from trichloroethylene in male B6C3F1 mice. Toxicol Appl Pharmacol. 1993 Nov;123(1):1-8. doi: 10.1006/taap.1993.1214.
• Background Gribble GW. Naturally occurring organohalogen compounds--a comprehensive survey. Fortschr Chem Org Naturst. 1996;68:1-423. No abstract available.
• Background Agbenyega T, Planche T, Bedu-Addo G, Ansong D, Owusu-Ofori A, Bhattaram VA, Nagaraja NV, Shroads AL, Henderson GN, Hutson AD, Derendorf H, Krishna S, Stacpoole PW. Population kinetics, efficacy, and safety of dichloroacetate for lactic acidosis due to severe malaria in children. J Clin Pharmacol. 2003 Apr;43(4):386-96. doi: 10.1177/0091270003251392.
• Background Yan Z, Henderson GN, James MO, Stacpoole PW. Determination of dichloroacetate and its metabolites in human plasma by gas chromatography-mass spectrometry. J Chromatogr B Biomed Sci Appl. 1997 Dec 5;703(1-2):75-84. doi: 10.1016/s0378-4347(97)00404-0.
• Background Jia M, Wu WW, Yost RA, Chadik PA, Stacpoole PW, Henderson GN. Simultaneous determination of trace levels of nine haloacetic acids in biological samples as their pentafluorobenzyl derivatives by gas chromatography/tandem mass spectrometry in electron capture negative ion chemical ionization mode. Anal Chem. 2003 Aug 15;75(16):4065-80. doi: 10.1021/ac034036w.
• Background Stacpoole PW, Moore GW, Kornhauser DM. Toxicity of chronic dichloroacetate. N Engl J Med. 1979 Feb 15;300(7):372. doi: 10.1056/NEJM197902153000726. No abstract available.
• Background Stacpoole PW, Barnes CL, Hurbanis MD, Cannon SL, Kerr DS. Treatment of congenital lactic acidosis with dichloroacetate. Arch Dis Child. 1997 Dec;77(6):535-41. doi: 10.1136/adc.77.6.535. No abstract available.
• Background Stacpoole PW, Harman EM, Curry SH, Baumgartner TG, Misbin RI. Treatment of lactic acidosis with dichloroacetate. N Engl J Med. 1983 Aug 18;309(7):390-6. doi: 10.1056/NEJM198308183090702.
• Background Stacpoole PW, Moore GW, Kornhauser DM. Metabolic effects of dichloroacetate in patients with diabetes mellitus and hyperlipoproteinemia. N Engl J Med. 1978 Mar 9;298(10):526-30. doi: 10.1056/NEJM197803092981002.
• Background Neiberger RE, George JC, Perkins LA, Theriaque DW, Hutson AD, Stacpoole PW. Renal manifestations of congenital lactic acidosis. Am J Kidney Dis. 2002 Jan;39(1):12-23. doi: 10.1053/ajkd.2002.29872.
• Background Ammini CV, Fernandez-Canon J, Shroads AL, Cornett R, Cheung J, James MO, Henderson GN, Grompe M, Stacpoole PW. Pharmacologic or genetic ablation of maleylacetoacetate isomerase increases levels of toxic tyrosine catabolites in rodents. Biochem Pharmacol. 2003 Nov 15;66(10):2029-38. doi: 10.1016/j.bcp.2003.07.002.
• Background Guo X, Dixit V, Liu H, Shroads AL, Henderson GN, James MO, Stacpoole PW. Inhibition and recovery of rat hepatic glutathione S-transferase zeta and alteration of tyrosine metabolism following dichloroacetate exposure and withdrawal. Drug Metab Dispos. 2006 Jan;34(1):36-42. doi: 10.1124/dmd.105.003996. Epub 2005 Sep 30.
• Background Holme E, Lindstedt S. Tyrosinaemia type I and NTBC (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione). J Inherit Metab Dis. 1998 Aug;21(5):507-17. doi: 10.1023/a:1005410820201.
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Drugs

Indications

No indication recorded.