PMID- 16162852
OWN - NLM
STAT- MEDLINE
DCOM- 20060110
LR  - 20131121
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 88
IP  - 2
DP  - 2005 Dec
TI  - Effect of N-acetylcysteine on lipopolysaccharide-induced intra-uterine fetal 
      death and intra-uterine growth retardation in mice.
PG  - 525-33
AB  - 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 microg/kg, ip) 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.
FAU - Xu, De-Xiang
AU  - Xu DX
AD  - Department of Toxicology, Anhui Medical University, Hefei, PR China. 
      xudex@mail.hf.ah.cn
FAU - Chen, Yuan-Hua
AU  - Chen YH
FAU - Wang, Hua
AU  - Wang H
FAU - Zhao, Lei
AU  - Zhao L
FAU - Wang, Jian-Ping
AU  - Wang JP
FAU - Wei, Wei
AU  - Wei W
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050914
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Lipopolysaccharides)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/administration & dosage/*pharmacology
MH  - Animals
MH  - Bone Development/drug effects
MH  - Bone and Bones/drug effects/embryology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Fetal Death/chemically induced/*prevention & control
MH  - Fetal Development/*drug effects
MH  - Fetal Growth Retardation/chemically induced/*prevention & control
MH  - Lipopolysaccharides/administration & dosage/*toxicity
MH  - Male
MH  - Maternal Exposure
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Pregnancy
EDAT- 2005/09/16 09:00
MHDA- 2006/01/13 09:00
CRDT- 2005/09/16 09:00
PHST- 2005/09/16 09:00 [pubmed]
PHST- 2006/01/13 09:00 [medline]
PHST- 2005/09/16 09:00 [entrez]
AID - kfi300 [pii]
AID - 10.1093/toxsci/kfi300 [doi]
PST - ppublish
SO  - Toxicol Sci. 2005 Dec;88(2):525-33. doi: 10.1093/toxsci/kfi300. Epub 2005 Sep 14.