Lin, S;
Wang, L;
Huang, Y;
Wang, Y;
Wang, C;
Greene, NDE;
Ren, A;
(2018)
Oxidative Stress and Apoptosis in Benzo[a]pyrene-Induced Neural Tube Defects.
Free Radical Biology and Medicine
, 116
pp. 149-158.
10.1016/j.freeradbiomed.2018.01.004.
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Abstract
Neural tube defects (NTDs) are among the most common and severe congenital malformations and result from incomplete closure of the neural tube during early development. Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to be a risk factor for NTDs and previous studies imply that the mechanism underlying the association between PAH exposure and NTDs may involve oxidative stress and apoptosis. The objectives of this study were to investigate whether there is a direct effect of maternal benzo[α] pyrene (BaP) exposure on the closure of the neural tube in mice, and to examine the underlying mechanisms by combining animal experiments and human subject studies. We found that intraperitoneal injection of BaP from embryonic day 7 at a dose of 250 mg kg-1 induced NTDs (13.3% frequency) in ICR mice. BaP exposure significantly increased expression of genes associated with oxidative stress, Cyp1a1, Sod1 and Sod2, while repressing Gpx1. Elevated apoptosis and higher protein expression of cleaved caspase-3 in the neuroepithelium of treated embryos were observed. Pre-treatment with vitamin E, added to food, significantly protected against BaP-induced NTDs (1.4% frequency) (P < 0.05). Vitamin E also partly normalized oxidative stress related gene expression and excess apoptosis in BaP-treated embryos. Examination of human neural tissues revealed that increased levels of protein carbonyl and apoptosis were related with maternal exposure to PAHs and the risk of NTDs. Collectively, these results suggest that BaP exposure could induce NTDs and that this may involve increased oxidative stress and apoptosis, while vitamin E may have a protective effect.
| Type: | Article |
|---|---|
| Title: | Oxidative Stress and Apoptosis in Benzo[a]pyrene-Induced Neural Tube Defects |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.freeradbiomed.2018.01.004 |
| Publisher version: | http://doi.org/10.1016/j.freeradbiomed.2018.01.004 |
| Language: | English |
| Additional information: | Copyright © 2018 The Authors. This work is licensed under a Creative Commons Attribution 4.0 International License. |
| Keywords: | Apoptosis, Benzo[a]pyrene, Neural tube defects, Oxidative stress, Polycyclic aromatic hydrocarbons, Vitamin E |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10041657 |
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