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.

Glutathione Peroxidase-Catalase Cooperativity Is Required for Resistance to Hydrogen Peroxide by Mature Rat Oligodendrocytes

“…Catalase immunoreactivity and activity were found to be higher in the neonatal rat than in the adult (Del Ma3stro and McDonald, 1987;Moreno et al, 1995;Hamby-Mason et al, 1997). In contrast, GPx was shown to undergo a 70% increase in activity in rat whole brain between birth and adulthood (Brannan et al, 1981).…”

Genetic polymorphism in ethanol metabolism: acetaldehyde contribution to alcohol abuse and alcoholism

“…48 Further studies have demonstrated that both Genetic polymorphism in ethanol metabolism E Quertemont astrocytes in culture and rat brain homogenates are able to produce biologically significant concentrations of acetaldehyde from perfused ethanol. 34,[49][50][51] These studies have also shown that catalase plays a critical role in this process, as the addition of various catalase inhibitors to brain homogenates reduces acetaldehyde accumulation after ethanol perfusion. 34,50 However, other pathways might also be involved in ethanol metabolism and acetaldehyde production within the brain.…”

Motor Stimulant Effects of Ethanol Injected into the Substantia Nigra Pars Reticulata: Importance of Catalase-Mediated Metabolism and the Role of Acetaldehyde

“…Some of the acetaldehyde present in the brain can be the result of acetaldehyde molecules that are produced peripherally and then reach the brain, although it is difficult for acetaldehyde to cross the blood-brain barrier because of the metabolic barrier presented by large concentrations of ALDH (Hunt, 1996;Quertemont and Tambour, 2004). Nevertheless, some acetaldehyde can be directly formed in the brain through the actions of catalase (Aragon et al, 1992b;Reddy et al, 1995;Zimatkin and Lindros, 1996;Hamby-Mason et al, 1997;Eysseric et al, 1997;Zimatkin et al, 1998). The notion that ethanol metabolism in the brain is important for some of the behavioral effects of ethanol is supported by the reports that manipulations of catalase activity exert a powerful effect on ethanol-induced behavior (Aragon et al, 1992a;Aragon and Amit, 1993;Correa et al, 1999aCorrea et al, , b, 2000Correa et al, , 2001Correa et al, , 2004aSanchis-Segura et al, 1999a-c;Pastor et al, 2002).…”