Fetal ethanol (E) exposure has well documented deleterious effects on brain development, yet it is uncertain if the neurotoxicity of maternal E consumption is generated by E itself, by its primary metabolite acetaldehyde (AcHO), or both. The current studies present evidence that homogenates of immature rat brains can generate ACHO via a catalase (CAT)-mediated reaction and that AcHO may be produced in vive by this system. Homogenates of day 19 fetal rat brain were incubated with E (50 mM). When incubated with CAT inhibitors (sodium azide or 3-aminotriazele), AcHO formation was blocked, whereas neither the alcohol dehydrogenase inhibitor, 4-methylpyrazole, nor p- 450 inhibitors decreased AcHe production. Three hours after one oral dose of E (4 g/kg to a pregnant dam (gestation day 19), AcHO levels in fetal brain increased to 14.28 ± 1.82 nM/g tissue. Baseline CAT activity in day 19 fetal brains was 4.5 times adult values (p < 0.05). Western blot analysis determined that CAT protein level in the day 19 fetal brain exceeded that in adult brain by 2.5 times. One hour after a single dose of E, CAT activity in day 19 fetal brain increased by 8.2 units/mg protein. In 5-day-old neonatal brains during the 'third trimester' brain growth spurt, baseline CAT activity was twice the adult values (p < 0.05) and a 2-day in vivo E regimen increased AcHe levels to four times the control values, with a concomitant 1.7-fold increase in CAT activity. This was prevented by administration of e CAT inhibitor (3-amino-1,2,4-triazole). Immunohistochemical staining of neonatal brains exposed to E illustrated the presence of acetaldehyde-protein adducts. We conclude that AcHO is likely produced in rat fetal and neonatal brain via CAT-mediated oxidation of E. This phenomenon may be an important factor in the neurotoxic effects of in utero E exposure.
|Original language||English (US)|
|Number of pages||10|
|Journal||Alcoholism: Clinical and Experimental Research|
|State||Published - 1997|
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Psychiatry and Mental health