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Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin.

Ma P, Liu X, Wu J, Yan B, Zhang Y, Lu Y, Wu Y, Liu C, Guo J, Nanberg E, Bornehag CG, Yang X - Sci Rep (2015)

Bottom Line: Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products.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.

View Article: PubMed Central - PubMed

Affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.

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.

No MeSH data available.


Related in: MedlinePlus

Potential mechanism of DINP-induced damage in mouse brains.DINP-induced adverse effects in mice brains occur through ROS generation and oxidative stress. Oxidative stress then induces cell damage in the brain, and learning memory and anxiety are altered are affected, whereas treatment with Mel protects cells by decreasing oxidative stress (Figure 10 was made by Xudong Liu and the different photographs of the mice were originally taken by Xudong Liu).
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f10: Potential mechanism of DINP-induced damage in mouse brains.DINP-induced adverse effects in mice brains occur through ROS generation and oxidative stress. Oxidative stress then induces cell damage in the brain, and learning memory and anxiety are altered are affected, whereas treatment with Mel protects cells by decreasing oxidative stress (Figure 10 was made by Xudong Liu and the different photographs of the mice were originally taken by Xudong Liu).

Mentions: This study aimed to examine the effect of DINP on the brains of mice, and to explore whether Mel could be used as a protective agent. Our results suggest that high concentrations of DINP (20 or 200 mg/kg/day) decreased the cognitive abilities and induced anxiety in mice. We concluded that DINP resulted in oxidative stress that caused damage to the mouse brain. Furthermore, Mel was confirmed as a protective agent having been shown to decrease oxidative stress levels (Fig. 10).


Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin.

Ma P, Liu X, Wu J, Yan B, Zhang Y, Lu Y, Wu Y, Liu C, Guo J, Nanberg E, Bornehag CG, Yang X - Sci Rep (2015)

Potential mechanism of DINP-induced damage in mouse brains.DINP-induced adverse effects in mice brains occur through ROS generation and oxidative stress. Oxidative stress then induces cell damage in the brain, and learning memory and anxiety are altered are affected, whereas treatment with Mel protects cells by decreasing oxidative stress (Figure 10 was made by Xudong Liu and the different photographs of the mice were originally taken by Xudong Liu).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4589782&req=5

f10: Potential mechanism of DINP-induced damage in mouse brains.DINP-induced adverse effects in mice brains occur through ROS generation and oxidative stress. Oxidative stress then induces cell damage in the brain, and learning memory and anxiety are altered are affected, whereas treatment with Mel protects cells by decreasing oxidative stress (Figure 10 was made by Xudong Liu and the different photographs of the mice were originally taken by Xudong Liu).
Mentions: This study aimed to examine the effect of DINP on the brains of mice, and to explore whether Mel could be used as a protective agent. Our results suggest that high concentrations of DINP (20 or 200 mg/kg/day) decreased the cognitive abilities and induced anxiety in mice. We concluded that DINP resulted in oxidative stress that caused damage to the mouse brain. Furthermore, Mel was confirmed as a protective agent having been shown to decrease oxidative stress levels (Fig. 10).

Bottom Line: Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products.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.

View Article: PubMed Central - PubMed

Affiliation: Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular and Metabolic Disorders, Hubei University of Science and Technology, Xianning 437100, China.

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.

No MeSH data available.


Related in: MedlinePlus