Skip Navigation



ToxSci Advance Access published online on September 14, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi300
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
88/2/525    most recent
kfi300v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Xu, D.-X.
Right arrow Articles by Wei, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Xu, D.-X.
Right arrow Articles by Wei, W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published by Oxford University Press 2005.
Received July 23, 2005
Accepted August 22, 2005

Reproductive and Developmental Toxicology

Effect of N-Acetylcysteine on Lipopolysaccharide-Induced Intra-Uterine Fetal Death and Intra-Uterine Growth Retardation in Mice

De-Xiang Xu 1*, Yuan-Hua Chen 2, Hua Wang 2, Lei Zhao 2, Jian-Ping Wang 2, and Wei Wei 3

1 Department of Toxicology, Anhui Medical University, Hefei, 230032, P. R. China; Key Laboratory of Anti-inflammatory and Immunopharmacology of Anhui Province, Hefei, 230032, P.R.China
2 Department of Toxicology, Anhui Medical University, Hefei, 230032, P. R. China
3 Key Laboratory of Anti-inflammatory and Immunopharmacology of Anhui Province, Hefei, 230032, P.R.China

* To whom correspondence should be addressed.
De-Xiang Xu, E-mail: xudex{at}mail.hf.ah.cn


  Abstract

Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR) and preterm delivery. Reactive oxygen species (ROS) have been associated with LPS-induced developmental toxicity. N-acetylcysteine (NAC) is a glutathione (GSH) precursor and direct antioxidant. The present study investigated the effects of NAC on LPS-induced IUFD and IUGR. All pregnant mice except controls were injected with LPS (75 µg/kg, i.p.) on gestational day (gd) 15-17. NAC was administered in two different modes. In mode A, the pregnant mice were pretreated with two doses of NAC (either 50 plus 25 mg/kg or 200 plus 100 mg/kg) before LPS, one (either 50 or 200 mg/kg) at 12 h before LPS and the other (either 25 or 100 mg/kg) at 15 min before LPS. In mode B, the pregnant mice were administered with two doses of NAC (either 50 plus 25 mg/kg or 200 plus 100 mg/kg) in 24 h, one (either 50 or 200 mg/kg) injected immediately after LPS and the other (either 25 or 100 mg/kg) injected 3 h after LPS. The number of live fetuses, dead fetuses and resorption sites was counted on gd 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were measured and skeletal development was evaluated. Results showed that pretreatment with NAC significantly alleviated LPS-induced fetal mortality and reversed LPS-induced growth and skeletal development retardation. Correspondingly, pretreatment with NAC significantly attenuated LPS-induced elevation in TNF-{alpha} concentration in maternal serum and amniotic fluid and lipid peroxidation in maternal and fetal livers. By contrast to pretreatment, posttreatment with NAC had no effect on LPS-induced TNF-{alpha} production and lipid peroxidation. When administered after LPS, NAC did not protect against LPS-induced IUFD and IUGR and in fact aggravated LPS-induced preterm labor. All these results indicate that NAC had a dual effect on LPS-induced IUFD and IUGR. Pretreatment with NAC improves fetal survival and reverses LPS-induced fetal growth and skeletal development retardation, whereas posttreatment with NAC aggravates LPS-induced preterm labor.

Keywords: N-acetylcysteine; lipopolysaccharide; intra-uterine fetal death; intra-uterine growth retardation.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
L. Zhao, Y.-H. Chen, H. Wang, Y.-L. Ji, H. Ning, S.-F. Wang, C. Zhang, J.-W. Lu, Z.-H. Duan, and D.-X. Xu
Reactive Oxygen Species Contribute to Lipopolysaccharide-Induced Teratogenesis in Mice
Toxicol. Sci., May 1, 2008; 103(1): 149 - 157.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.