Brain ethanol-metabolizing enzymes are differentially expressed in lead-exposed animals after voluntary ethanol consumption: Pharmacological approaches.
Neurotoxicology
; 75: 174-185, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31550440
ABSTRACT
Developmentally-lead (Pb)-exposed rats showed an enhanced vulnerability to the stimulating and motivational effects of ethanol (EtOH). This is accompanied by differential activity of the brain EtOH-metabolizing enzymes catalase (CAT) and mitochondrial aldehyde dehydrogenase (ALDH2). Based on the theory that brain acetaldehyde accumulation is associated with the reinforcing properties of EtOH, this study sought to determine brain CAT and ALDH2 expression in limbic areas of control and Pb-exposed animals after voluntary EtOH intake. Thirty-five-day-old rats perinatally exposed to 220â¯ppm Pb were offered with water or increasing EtOH solutions (2-10% v/v) during 28 days until postnatal day (PND) 63. Once intake was stable, the animals were administered 1) saline (SAL; test days 21-24 or 21-28, as corresponds), or 2) a CAT inhibitor 3-amine 1, 2, 4-triazole (AT; 250â¯mg/kg intraperitoneally [i.p.], 5â¯h before the last eight EtOH intake sessions -test days 21-24 and 25-28), or 3) a CAT booster 3-nitropropionic acid (3NPA; 20â¯mg/kg subcutaneously [s.c.], 45â¯min before the last four EtOH intake sessions -test days 25-28). Two additional groups were centrally-administered cyanamide (CY, an ALDH2 inhibitor, 0.3â¯mg i.c.v. immediately before the last four EtOH sessions, test days 25-28) or its corresponding vehicle (VEH). Lead exposure increased EtOH intake, an effect potentiated in both groups by 3NPA or CY pretreatments and reduced by AT, albeit selectivity in the Pb group. Catalase abundance in limbic areas parallels these observations in the Pb group, showing higher CAT expression in all areas after EtOH consumption respect to the controls, an effect prevented by AT administration. In contrast, ALDH2 expression was reduced in the Pb animals after EtOH intake, with CY potentiating this effect in all brain areas under study. Based on these results and on previous evidences, we suggest that Pb exposure promotes acetaldehyde accumulation in limbic regions, providing some insights into the mechanism of action that underlies the vulnerability to the excessive EtOH consumption reported in these animals.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Intoxicação do Sistema Nervoso por Chumbo
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Etanol
Limite:
Animals
Idioma:
En
Revista:
Neurotoxicology
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Argentina