title: Catalase mediates acetaldehyde formation from ethanol in fetal and neonatal rat brain.
abstract: 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 vivo 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-aminotriazole), AcHO formation was blocked, whereas neither the alcohol dehydrogenase inhibitor, 4-methylpyrazole, nor P-450 inhibitors decreased AcHO 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 AcHO levels to four times the control values, with a concomitant 1.7-fold increase in CAT activity. This was prevented by administration of a 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.
authors.affiliation: Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7878, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hamby-Mason
authors.forename: J J
authors.initials: JJ
authors.lastname: Chen
authors.forename: S
authors.initials: S
authors.lastname: Schenker
authors.forename: A
authors.initials: A
authors.lastname: Perez
authors.forename: G I
authors.initials: GI
authors.lastname: Henderson
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology* / Q000201:enzymology; D002374:Catalase / Q000502:physiology*; D000431:Ethanol / Q000493:pharmacokinetics* / Q000633:toxicity; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000196:embryology* / Q000201:enzymology; D005865:Gestational Age; D007124:Immunoenzyme Techniques; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000431:Ethanol; D002374:Catalase; D000079:Acetaldehyde