title: Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin.
abstract: Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200 mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-а] and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50 mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects.
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ma
authors.affiliation: Lab. of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, China.|Department of Food science and Engineering, Moutai University, Renhuai 564500, China.
authors.forename: Xudong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.
authors.forename: Jiliang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Lab. of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Yan
authors.affiliation: Lab. of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, China.|Department of Food science and Engineering, Moutai University, Renhuai 564500, China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Lab. of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Lab. of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, China.
authors.forename: Junhui
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Health Sciences, Karlstad University, Karlstad, Sweden.
authors.forename: Eewa
authors.initials: E
authors.lastname: Nanberg
authors.affiliation: Department of Health Sciences, Karlstad University, Karlstad, Sweden.
authors.forename: Carl-Gustaf
authors.initials: CG
authors.lastname: Bornehag
authors.affiliation: Lab. of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan 430079, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000517:prevention & control*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D053148:Caspase 3 / Q000378:metabolism; D003072:Cognition Disorders / Q000139:chemically induced / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D010795:Phthalic Acids
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010795:Phthalic Acids; C528900:glial fibrillary astrocytic protein, mouse; C012125:diisononyl phthalate; C505409:Casp3 protein, mouse; D053148:Caspase 3; D008550:Melatonin