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Combined use of vitamin E and nimodipine ameliorates dibutyl phthalate-induced memory deficit and apoptosis in mice by inhibiting the ERK 1/2 pathway.
- Source :
-
Toxicology & Applied Pharmacology . Apr2019, Vol. 368, p1-17. 17p. - Publication Year :
- 2019
-
Abstract
- Abstract Learning disabilities (LDs) in children are a serious global problem. Dibutyl phthalate (DBP), a plasticizer widely used in daily life, has been linked to triggering childhood LDs, however the mechanism underlying this remains unclear. Studies have shown that the ERK 1/2 pathway is closely related to apoptosis of hippocampal neurons. On the basis of these links between LDs, DBP and the ERK 1/2 pathway, we explore whether DBP induces hippocampal neuron apoptosis and increases behavioral disorders in mice via the ERK 1/2 pathway. We looked at oxidative stress, examined the calcium signal, detected the ERK 1/2 pathway and evaluated apoptosis as well as using histological observations, and found that DBP significantly increased oxidative damage and apoptosis in hippocampal neurons via the ERK 1/2 pathway in mice. We also found that pretreatment with the dihydropyridine's (DHP's) Ca2+ antagonist, nimodipine (NMDP), combined with the antioxidant Vitamin E (VE), attenuated ERK 1/2 phosphorylation and DBP-mediated disorders, suggesting that a combined use of VE and NMDP can ameliorate DBP-induced memory deficit and apoptosis via inhibiting the ERK 1/2 pathway. These results indicate that DBP predisposes oxidative damage and apoptosis in hippocampal neurons by activation of the ERK 1/2 pathway, and may be proposed as a possible mechanism underlying LDs in children. Moreover, VE and NMDP may play a certain protective role in the targeted treatment of childhood LDs. Graphical abstract Unlabelled Image Highlights • DBP induces apoptosis of hippocampal neurons via the ERK 1/2 pathway. • DBP activates the ERK 1/2 pathway through ROS accumulation and excessive Ca2+. • VE and NMDP can ameliorate DBP-induced apoptosis by inhibiting the ERK 1/2 pathway. [ABSTRACT FROM AUTHOR]
- Subjects :
- *VITAMIN E
*NIMODIPINE
*DIBUTYL phthalate
*APOPTOSIS
*DIHYDROPYRIDINE
Subjects
Details
- Language :
- English
- ISSN :
- 0041008X
- Volume :
- 368
- Database :
- Academic Search Index
- Journal :
- Toxicology & Applied Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 135053831
- Full Text :
- https://doi.org/10.1016/j.taap.2019.02.008