PMID- 20006703
OWN - NLM
STAT- MEDLINE
DCOM- 20100615
LR  - 20141120
IS  - 1872-9738 (Electronic)
IS  - 0892-0362 (Linking)
VI  - 32
IP  - 2
DP  - 2010 Mar-Apr
TI  - Differential effects of chronic ethanol exposure on cytochrome P450 2E1 and the 
      hypothalamic-pituitary-adrenal axis in the maternal-fetal unit of the guinea pig.
PG  - 164-70
LID - 10.1016/j.ntt.2009.12.002 [doi]
AB  - BACKGROUND: Ethanol neurobehavioural teratogenicity is a leading cause of 
      developmental mental deficiency, in which the hippocampus is a target site of 
      injury. The multi-faceted mechanism of ethanol teratogenicity is not completely 
      understood. This study tested the hypothesis that chronic ethanol exposure (CEE), 
      via chronic maternal ethanol administration, increases cytochrome P450 2E1 
      (CYP2E1) expression and alters hypothalamic-pituitary-adrenal (HPA) axis activity 
      in the maternal-fetal unit during the third-trimester-equivalent of gestation. 
      METHODS: Pregnant Dunkin-Hartley-strain guinea pigs received daily oral 
      administration of ethanol (4 g ethanol/kg maternal body weight) or 
      isocaloric-sucrose/pair-feeding (control) throughout gestation (term, about 
      gestational day (GD) 68). On GD 45, 55 and 65, pregnant animals were euthanized 
      2h after the last daily dose. Maternal and fetal body weights and fetal 
      hippocampal brain weight were determined. Maternal and fetal samples were 
      collected for the determination of liver CYP2E1 enzymatic activity and plasma 
      free cortisol and ACTH concentrations. RESULTS: CEE, with maternal blood ethanol 
      concentration of 108-124 mg/dl at 2h after the last dose, decreased fetal 
      hippocampal weight only at GD 65 and had no effect on fetal body weight compared 
      with control. CYP2E1 activity increased with gestational age in the fetal liver 
      microsomal and mitochondrial fractions. CEE increased CYP2E1 activity in the 
      microsomal and mitochondrial fractions of maternal liver at the three gestational 
      ages and in both hepatic subcellular fractions of the GD 65 fetus compared with 
      control. There was a gestational-age-dependent increase in maternal and fetal 
      plasma free cortisol concentrations, but no effect of CEE compared with control. 
      Maternal and fetal plasma ACTH concentrations were unaffected by CEE compared 
      with control, and were virtually unchanged during the third-trimester-equivalent 
      that was studied. CONCLUSION: These data demonstrate that, in the pregnant guinea 
      pig, this CEE regimen increases liver CYP2E1 activity, without affecting HPA axis 
      function, in the maternal-fetal unit during near-term gestation. The CEE-induced 
      increase in liver CYP2E1 activity and potential oxidative stress in the 
      maternal-fetal unit may play a role in the pathogenesis of ethanol 
      teratogenicity.
CI  - Copyright (c) 2009 Elsevier Inc. All rights reserved.
FAU - Hewitt, Amy J
AU  - Hewitt AJ
AD  - Department of Pharmacology and Toxicology, Queen's University, Kingston, ON, 
      Canada.
FAU - Walker, Kevin R
AU  - Walker KR
FAU - Kobus, Susan M
AU  - Kobus SM
FAU - Poklewska-Koziell, Margo
AU  - Poklewska-Koziell M
FAU - Reynolds, James N
AU  - Reynolds JN
FAU - Brien, James F
AU  - Brien JF
LA  - eng
GR  - MOP-81185/Canadian Institutes of Health Research/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091216
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - EC 1.14.13.- (Cytochrome P-450 CYP2E1)
SB  - IM
MH  - Alcohol-Induced Disorders, Nervous System/*metabolism/physiopathology
MH  - Animals
MH  - Child, Preschool
MH  - Cognition Disorders/*chemically induced/physiopathology
MH  - Cytochrome P-450 CYP2E1/*drug effects/metabolism
MH  - Developmental Disabilities/chemically induced/metabolism/physiopathology
MH  - Disease Models, Animal
MH  - Drug Administration Schedule
MH  - Energy Metabolism/drug effects/physiology
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/*metabolism/physiopathology
MH  - Guinea Pigs
MH  - Humans
MH  - Hypothalamo-Hypophyseal System/*drug effects/physiopathology
MH  - Liver/drug effects/metabolism/physiopathology
MH  - Microsomes, Liver/drug effects/metabolism
MH  - Mitochondria/drug effects/metabolism
MH  - Oxidative Stress/drug effects/physiology
MH  - Pituitary-Adrenal System/*drug effects/physiopathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/metabolism/physiopathology
EDAT- 2009/12/17 06:00
MHDA- 2010/06/16 06:00
CRDT- 2009/12/17 06:00
PHST- 2009/08/18 00:00 [received]
PHST- 2009/11/07 00:00 [revised]
PHST- 2009/12/07 00:00 [accepted]
PHST- 2009/12/17 06:00 [entrez]
PHST- 2009/12/17 06:00 [pubmed]
PHST- 2010/06/16 06:00 [medline]
AID - S0892-0362(09)00201-3 [pii]
AID - 10.1016/j.ntt.2009.12.002 [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 2010 Mar-Apr;32(2):164-70. doi: 10.1016/j.ntt.2009.12.002. 
      Epub 2009 Dec 16.