HEME OXYGENASE ACTIVITY AND ACUTE AND CHRONIC ETHANOL EXPOSURE IN THEHIPPOCAMPUS, FRONTAL CEREBRAL-CORTEX, AND CEREBELLUM OF THE NEAR-TERMFETAL 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 th is study was to determine the effects of in vitro, acute in vivo, and chronic in vivo ethanol exposure on HO activity in the hippocampus, fr ontal cerebral cortex, and cerebellum of the near-term fetal guinea pi g. HO activity was determined using a gas chromatographic method to qu antitate CO formation in the microsomal fraction of the homogenate of each selected brain region, incubated with saturating concentrations o f heme, NADPH, and O-2. 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 th e fetal guinea pig at gestational day (GD) 62 (term, about GD 68). Acu te 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 s ucrose or water). For chronic daily maternal oral administration of 4 g ethanol/kg maternal body weight throughout gestation, fetal body, br ain, hippocampal, and cerebellar weights were decreased at GD 62 compa red with isocaloric-sucrose/pair-fed and water treatment control group s. Further more, isocaloric-sucrose/pair-feeding treatment decreased f etal 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 firs t study of the effect of ethanol exposure on HO activity in the develo ping brain of any species. The data demonstrate, for ethanol CNS terat ogenesis in the guinea pig manifesting as fetal brain growth restricti on, there is no associated change in HO activity in the hippocampus, f rontal cerebral cortex, or cerebellum. (C) 1997 Elsevier Science Inc.