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Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, 14676Article in journal (Refereed) PublishedText
Abstract [en]

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 200â 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-Crossed D sign°[ 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 (50â 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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2015. Vol. 5, 14676
Keyword [en]
Immunohistochemistry, Risk factors
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Research subject
Public Health Science
URN: urn:nbn:se:kau:diva-42349DOI: 10.1038/srep14676ScopusID: 2-s2.0-84942938338OAI: diva2:933881
Available from: 2016-06-07 Created: 2016-05-23 Last updated: 2016-06-07Bibliographically approved

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Nanberg, EewaBornehag, Carl Gustaf
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