title: Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats.
abstract: The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), γ-glutamylcysteine synthetase (γ-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at -80°C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12month old rats. These results indicate changes in OS parameters with age and toluene exposure resulted in oxidative damage in frontal cortex and cerebellum of 12 month old rats. Although increases in oxidative damage are associated with increases in horizontal motor activity in older rats, further research is warranted to determine if these changes in OS parameters are related to neurobehavioral and neurophysiological effects of toluene in animal models of aging.
authors.affiliation: Neurotoxicology Branch, Toxicity Assessment Division, NHEERL, ORD, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA. kodavanti.prasada@epa.gov
authors.forename: Prasada Rao S
authors.initials: PR
authors.lastname: Kodavanti
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Royland
authors.forename: Judy E
authors.initials: JE
authors.lastname: Richards
authors.forename: Jonathan
authors.initials: J
authors.lastname: Besas
authors.forename: Robert C
authors.initials: RC
authors.lastname: Macphail
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D011914:Rats, Inbred BN; D017382:Reactive Oxygen Species / Q000378:metabolism; D014050:Toluene / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D014050:Toluene