Heme oxygenase activity and acute and chronic ethanol exposure in the hippocampus, frontal cerebral cortex, and cerebellum of the near-term fetal guinea pig.
Heme oxygenase (HO) catalyzes the oxidation of heme to produce carbon monoxide, which is considered to be a novel neuronal messenger in the brain and may play a role in neuronal development. The objective of this study was to determine the effects of in vitro, acute in vivo, and chronic in vivo ethanol exposure on HO activity in the hippocampus, frontal cerebral cortex, and cerebellum of the near-term fetal guinea pig. HO activity was determined using a gas chromatographic method to quantitate CO formation in the microsomal fraction of the homogenate of each selected brain region, incubated with saturating concentrations of heme, NADPH, and O2. Fetal body, brain, hippocampal, and cerebellar weights were recorded. In vitro ethanol exposure (25-100 mM) did not affect hippocampal, cerebral cortical, or cerebellar HO activity of the fetal guinea pig at gestational day (GD) 62 (term, about GD 68). Acute maternal oral administration of 4 g ethanol/kg maternal body weight at GD 62 did not affect HO activity in these three fetal brain areas compared with control fetuses (maternal administration of isocaloric sucrose or water). For chronic daily maternal oral administration of 4 g ethanol/kg maternal body weight throughout gestation, fetal body, brain, hippocampal, and cerebellar weights were decreased at GD 62 compared with isocaloric-sucrose/pair-fed and water treatment control groups. Furthermore, isocaloric-sucrose/pair-feeding treatment decreased fetal body and brain weights compared with water treatment. Chronic in vivo ethanol exposure did not alter HO activity in the near-term fetal hippocampus, frontal cerebral cortex, or cerebellum. This is the first study of the effect of ethanol exposure on HO activity in the developing brain of any species. The data demonstrate, for ethanol CNS teratogenesis in the guinea pig manifesting as fetal brain growth restriction, there is no associated change in HO activity in the hippocampus, frontal cerebral cortex, or cerebellum.
Cook
M N
MN
Department of Pharmacology and Toxicology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada.
Marks
G S
GS
Vreman
H J
HJ
Nakatsu
K
K
Stevenson
D K
DK
Brien
J F
JF
D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D019422:Dietary Sucrose / Q000008:administration & dosage; D002149:Energy Intake; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D005625:Frontal Lobe / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D005865:Gestational Age; D006168:Guinea Pigs; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D009929:Organ Size; D011247:Pregnancy
D019422:Dietary Sucrose; D000431:Ethanol; D006419:Heme Oxygenase (Decyclizing)