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Neurotoxicology


Title:Acute and subchronic toxicity of inhaled toluene in male Long-Evans rats: Oxidative stress markers in brain
Author(s):Kodavanti PR; Royland JE; Moore-Smith DA; Besas J; Richards JE; Beasley TE; Evansky P; Bushnell PJ;
Address:"Neurotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. Electronic address: kodavanti.prasada@epa.gov. Genetic and Cellular Toxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. Neurotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. Cardiopulmonary and Immunotoxicology Branch, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. Inhalation Toxicology Facility, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA"
Journal Title:Neurotoxicology
Year:2015
Volume:20150903
Issue:
Page Number:10 - 19
DOI: 10.1016/j.neuro.2015.09.001
ISSN/ISBN:1872-9711 (Electronic) 0161-813X (Linking)
Abstract:"The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute and one subchronic, were conducted to seek effects of the VOC, toluene, in rats and to compare the effects between acute and subchronic exposures. Adult male Long-Evans rats were exposed to toluene vapor (n=6 per group) at a concentration of 0 or 1019 +/- 14 ppm for 6h in the acute study and at 0 +/- 0, 10 +/- 1.4, 97 +/- 7, or 995 +/- 43 ppm for 6h/d, 5d/week for 13 weeks in the subchronic study. For the acute study, brains were dissected on ice within 30 min of the end of exposure, while for the subchronic study, brains were dissected 18 h after the last exposure. Frontal cortex, hippocampus, cerebellum, and striatum were assayed for a variety of oxidative stress (OS) parameters including total aconitase (TA), protein carbonyls, glutathione peroxidase (GPX), glutathione reductase (GRD), glutathione transferase (GST), gamma-glutamylcysteine synthetase (GCS), superoxide dismutase (SOD), total antioxidants (TAS), NADPH quinone oxidoreductase-1 (NQO1), and NADH ubiquinone reductase (UBIQ-RD) activities using commercially available kits. Following acute exposure, UBIQ-RD, GCS and GRD were increased significantly only in the cerebellum, while TAS was increased in frontal cortex. On the other hand, subchronic exposure affected several OS markers including increases in NQO1 and UBIQ-RD. The effect of subchronic toluene exposure on SOD and TAS was greater in the striatum than in the other brain regions. TA activity (involved in maintaining iron homeostasis and an indicator of DNA damage) was inhibited in striatum and cerebellum, increased in hippocampus, and unchanged in frontal cortex. Protein carbonyls increased significantly in both the frontal cortex and cerebellum. In general, the results showed that acute exposure to toluene affected OS parameters to a lesser extent than did subchronic exposure. These results suggest that toluene exposure induces OS in the brain and this may be a component of an adverse outcome pathway for some of the neurotoxic effects reported following toluene exposure"
Keywords:"Administration, Inhalation Animals Antioxidants/analysis Brain/*drug effects/*metabolism Male Oxidative Stress/*drug effects Rats Rats, Long-Evans Toluene/administration & dosage/*toxicity Aconitase Antioxidants Neurotoxicity Oxidative stress Protein carb;"
Notes:"MedlineKodavanti, Prasada Rao S Royland, Joyce E Moore-Smith, Debra A Besas, Jonathan Richards, Judy E Beasley, Tracey E Evansky, Paul Bushnell, Philip J eng Netherlands 2015/09/08 Neurotoxicology. 2015 Dec; 51:10-9. doi: 10.1016/j.neuro.2015.09.001. Epub 2015 Sep 3"

 
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