title: The effects of mixtures of dichloroacetate and trichloroacetate on induction of oxidative stress in livers of mice after subchronic exposure.
abstract: Dichloroacetate (DCA) and trichloroacetate (TCA) are drinking-water chlorination by-products previously found to induce oxidative stress (OS) in hepatic tissues of B6C3F1 male mice. To assess the effects of mixtures of the compounds on OS, groups of male B6C3F1 mice were treated daily by gavage with DCA at doses of 7.5, 15, or 30 mg/kg/d, TCA at doses of 12.5, 25, or 50 mg/kg/d, and 3 mixtures of DCA and TCA (Mix I, Mix II, and Mix III), for 13 wk. The concentrations of the compounds in Mix I, Mix II, and Mix III corresponded to those producing approximately 15, 25, and 35%, respectively, of maximal induction of OS by individual compounds. Livers were assayed for production of superoxide anion (SA), lipid peroxidation (LP), and DNA single-strand breaks (SSB). DCA, TCA, and the mixtures produced dose-dependent increases in the three tested biomarkers. Mix I and II effects on the three biomarkers, and Mix III effect on SA production were found to be additive, while Mix III effects on LP and DNA-SSB were shown to be greater than additive. Induction of OS in livers of B6C3F1 mice after subchronic exposure to DCA and TCA was previously suggested as an important mechanism in chronic hepatotoxicity/hepatocarcinogenicity induced by these compounds. Hence, there may be rise in exposure risk to these compounds as these agents coexist in drinking water.
authors.affiliation: a College of Pharmacy and Pharmaceutical Sciences , University of Toledo , Toledo , Ohio , USA.
authors.forename: Ezdihar
authors.initials: E
authors.lastname: Hassoun
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Cearfoss
authors.forename: Sukamto
authors.initials: S
authors.lastname: Mamada
authors.forename: Noor
authors.initials: N
authors.lastname: Al-Hassan
authors.forename: Michael
authors.initials: M
authors.lastname: Brown
authors.forename: Kevin
authors.initials: K
authors.lastname: Heimberger
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded / Q000187:drug effects; D003999:Dichloroacetic Acid / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D054879:Halogenation; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000187:drug effects*; D012044:Regression Analysis; D013481:Superoxides / Q000378:metabolism; D014238:Trichloroacetic Acid / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical; D013481:Superoxides; D014238:Trichloroacetic Acid; D003999:Dichloroacetic Acid