title: Increased oxidative stress in the liver of mice treated with trichloroethylene.
abstract: In this study the trichloroethylene treatment-associated production of oxidative stress in mouse liver by measurements of changes in oxygen consumption, the disappearance of beta-nicotinamide adenine dinucleotide reduced form (NADPH), and the rate of malondialdehyde formation have been investigated. The treatment of mice with trichloroethylene (TCE), trichloroacetic acid (TCA), a metabolite of TCE, or clofibrate, a peroxisome proliferator, resulted in an increase in the oxygen consumption of liver microsomes compared to the values of the untreated controls. A maximum increase in the level of oxygen consumption in liver microsomes was observed in the mice treated with TCE, followed by clofibrate and TCA treatments. All three agents also increased the rate of NADPH oxidation in mice liver microsomes compared with untreated controls. NADPH oxidation was increased four fold by TCE or clofibrate (38 or 37 nmol/min) and two fold by TCA treatment (17 nmol/min) over that of the control animals (9 nmol/min). The concentration of malondialdehyde was higher in all three treated groups in comparison with control values. Malondialdehyde levels were elevated by 227%, 191%, and 118% by treatment with TCE, clofibrate, and TCA, respectively. Increases in the levels of oxygen consumption, NADPH disappearance, and malondialdehyde production in microsomes from liver of mice treated chronically with TCE or TCA are all indicative of elevated levels of oxidative stress. Increased oxidative stress may be involved in the induction of TCE-associated hepatotoxicity.
authors.affiliation: Department of Environmental Health Sciences, University of Alabama, Birmingham 35294.
authors.forename: A
authors.initials: A
authors.lastname: Atkinson
authors.forename: R G
authors.initials: RG
authors.lastname: Meeks
authors.forename: D
authors.initials: D
authors.lastname: Roy
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D002994:Clofibrate / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D014238:Trichloroacetic Acid / Q000494:pharmacology; D014241:Trichloroethylene / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D014241:Trichloroethylene; D008315:Malondialdehyde; D009249:NADP; D014238:Trichloroacetic Acid; D002994:Clofibrate