title: Inflammatory and oxidative stress-related effects associated with neurotoxicity are maintained after exclusively prenatal trichloroethylene exposure.
abstract: Trichloroethylene (TCE) is a widespread environmental toxicant with immunotoxic and neurotoxic potential. Previous studies have shown that continuous developmental exposure to TCE encompassing gestation and early life as well as postnatal only exposure in the drinking water of MRL+/+ mice promoted CD4+T cell immunotoxicity, glutathione depletion and oxidative stress in the cerebellum, as well increased locomotor activity in male offspring. The purpose of this study was to characterize the effects of exclusively prenatal exposure on these parameters. Another goal was to investigate potential plasma oxidative stress/inflammatory biomarkers to possibly be used as predictors of TCE-mediated neurotoxicity. In the current study, 6 week old male offspring of dams exposed gestationally to 0, 0.01, and 0.1mg/ml TCE in the drinking water were evaluated. Our results confirmed that the oxidized phenotype in plasma and cerebellum was maintained after exclusively prenatal exposure. A Phenotypic analysis by flow cytometry revealed that TCE exposure expanded the effector/memory subset of peripheral CD4+T cells in association with increased production of pro-inflammatory cytokines IFN-γ and IL-17. Serum biomarkers of oxidative stress and inflammation were also elevated in plasma suggesting that systemic effects are important and may be used to predict neurotoxicity in our model. These results suggested that the prenatal period is a critical stage of life by which the developing CNS and immune system are susceptible to long-lasting changes mediated by TCE.
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children's Hospital Research Institute, 13 Children's Way, Little Rock, AR 72202, USA. Electronic address: blossomsarah@uams.edu.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Blossom
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children's Hospital Research Institute, 13 Children's Way, Little Rock, AR 72202, USA.
authors.forename: Stepan B
authors.initials: SB
authors.lastname: Melnyk
authors.affiliation: Department of Pediatrics, University of Arkansas for Medical Sciences, College of Medicine, Arkansas Children's Hospital Research Institute, 13 Children's Way, Little Rock, AR 72202, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, College of Medicine, 4301 West Markham St., Little Rock, AR 72205, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Wessinger
authors.affiliation: Department of Research and Development, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Cooney
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000209:etiology*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D007530:Isoflurane / Q000633:toxicity; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics; D014241:Trichloroethylene / Q000633:toxicity*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D016207:Cytokines; C507114:Gpr84 protein, mouse; D043562:Receptors, G-Protein-Coupled; D014241:Trichloroethylene; C002744:3-nitrotyrosine; D014443:Tyrosine; D007530:Isoflurane
keywords: Behavior; Cerebellum; Glutathione; Inflammation; Redox; Trichloroethylene oxidative stress
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