Pretreatment with N-acetyl cysteine suppresses chronic reactive astrogliosis following maternal nanoparticle exposure during gestational period

Abstract

Early pregnant employees are potentially and unintendedly exposed to industrial chemicals including nanoparticles. Developmental toxicity of nanoparticle exposure has been concerned because exposure to fine particle including carbon black nanoparticle (CB-NP) during the brain developmental stage enhances the risk of brain disorders. Maternal CB-NP exposure dose-dependently induces astrogliosis, which is an abnormal increase in the reactive astrocytes with glial fibrillary acidic protein (GFAP) and aquaporin-4 overexpression due to the destruction of nearby neurons and blood vessels. The present study aimed to investigate protective effects of antioxidants on the histopathological denaturation with astrogliosis following maternal CB-NP exposure in offspring mice, thereby to evaluate the role of oxidative stress on the developmental toxicity. Pregnant ICR mice were treated with CB-NP by intranasal instillation on gestational days 5 and 9. N-acetyl cysteine (NAC) or ascorbic acid was intraperitoneally administered to the pregnant mice 1 h prior to CB-NP instillation. The brains were collected from 6- to 12-week-old offspring mice and analyzed using western blotting and immunohistochemistry. NAC suppressed GFAP overexpression in 6- and 12-week-old offspring mice following maternal CB-NP exposure. However, NAC did not suppress aquaporin-4 overexpression following maternal CB-NP exposure. Ascorbic acid did not suppress, but rather slightly and significantly enhanced the expression of GFAP and aquaporin-4. These results indicate that astrogliosis by maternal CB-NP exposure is partially prevented by NAC pretreatment. Oxidative stress is a possible key factor of developmental neurotoxicity of maternal NP exposure. This study will contribute to elucidating the mechanisms underlying the effects of developmental neurotoxicity of NPs.

Keywords:

• Carbon black nanoparticle
• maternal exposure
• astrogliosis
• N-acetyl cysteine
• ascorbic acid

Acknowledgements

We would like to thank Mr Rikio Niki and Ms Rie Numazaki (Tokyo University of Science) for their technical assistance, and Prof. Yasser El-Sayed and Prof. Hazem Shaheen (Damanhour University) for their valuable discussion.

Disclosure statement

None of the authors have any competing interests related to this manuscript.

Additional information

Funding

This work was supported by a Grant-in Aid from the MEXT-Supported Program for the Strategic Research Foundation at Private Universities [grant number S1101015, 2011-2015] and a Grant-in-Aid from the Japan Society for the Promotion of Science (JSPS) Research Fellow [grant number 15J05718, 2015-2017]. The funders had no role in the preparation of the manuscript or the decision to publish it.