PMID- 18442069
OWN - NLM
STAT- MEDLINE
DCOM- 20090413
LR  - 20181201
IS  - 1522-7278 (Electronic)
IS  - 1520-4081 (Linking)
VI  - 24
IP  - 1
DP  - 2009 Feb
TI  - Growth retardation of fetal rats exposed to nicotine in utero: possible 
      involvement of CYP1A1, CYP2E1, and P-glycoprotein.
PG  - 33-42
LID - 10.1002/tox.20391 [doi]
AB  - To elucidate the possible metabolic mechanism of intrauterine growth retardation 
      induced by nicotine, this study determines the effects of prenatal nicotine 
      exposure on fetal development and cytochrome P4501A1 (CYP1A1), CYP2E1, and 
      P-glycoprotein (Pgp) expression in maternal liver and placenta. Pregnant rats 
      were given 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 
      (GD) 8 to GD 15, 18, or 21. In nicotine-treated groups, fetal developmental 
      parameters including body weight were significantly lower. The activities of 
      CYP1A1 and CYP2E1 in maternal liver microsomes in nicotine-treated groups 
      increased significantly with progressing gestation when compared with the 
      corresponding control, but returned to the level similar to the control in late 
      pregnancy. Nicotine-treated groups induced pathological changes and increased 
      malondialdehyde (MDA) content in the placenta when compared with the control. The 
      gene expressions of CYP1A1 and CYP2E1 in the placenta increased significantly in 
      nicotine-treated groups on GD 15 and GD 18, but returned to the level similar to 
      the corresponding control on GD 21. In nicotine group, there was a decrease of 
      mdr1a expression on GD 15, GD 18, and GD 21, with the most significant decrease 
      on GD 15. In contrast, no significant difference was found in mdr1b mRNA 
      expression between the nicotine-treated animals and the corresponding control. In 
      comparison with the corresponding control, the placental Pgp protein 
      significantly decreased on GD 15 and GD 18. Our results showed that prenatal 
      nicotine exposure resulted in inhibition of fetal growth significantly. The 
      induction of CYP2E1 and CYP1A1 gene expression by nicotine in the maternal liver 
      and placenta may be involved with the observed increase in oxidative stress and 
      lipid peroxidation. The inhibition of the placental Pgp expression by nicotine 
      may also contribute to an increased susceptibility of the fetus to environmental 
      toxins.
FAU - Wang, Ting
AU  - Wang T
AD  - Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 
      430071, China. clbwhcbd@yahoo.com
FAU - Chen, Man
AU  - Chen M
FAU - Yan, You-E
AU  - Yan YE
FAU - Xiao, Feng-Qin
AU  - Xiao FQ
FAU - Pan, Xiao-Liang
AU  - Pan XL
FAU - Wang, Hui
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Environ Toxicol
JT  - Environmental toxicology
JID - 100885357
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (RNA, Messenger)
RN  - 6M3C89ZY6R (Nicotine)
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2E1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/*metabolism
MH  - Animals
MH  - Body Weight/drug effects
MH  - Cytochrome P-450 CYP1A1/genetics/*metabolism
MH  - Cytochrome P-450 CYP2E1/genetics/*metabolism
MH  - Female
MH  - Fetus/*drug effects/*embryology/pathology
MH  - Gene Expression
MH  - Immunohistochemistry
MH  - Liver/drug effects/enzymology
MH  - Male
MH  - Nicotine/administration & dosage/*adverse effects
MH  - Placenta/drug effects/enzymology
MH  - Pregnancy
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Specific Pathogen-Free Organisms
EDAT- 2008/04/30 09:00
MHDA- 2009/04/14 09:00
CRDT- 2008/04/30 09:00
PHST- 2008/04/30 09:00 [pubmed]
PHST- 2009/04/14 09:00 [medline]
PHST- 2008/04/30 09:00 [entrez]
AID - 10.1002/tox.20391 [doi]
PST - ppublish
SO  - Environ Toxicol. 2009 Feb;24(1):33-42. doi: 10.1002/tox.20391.