RESUMO
BACKGROUND: This study was designed to investigate the relationship between the ethanol-oxidizing capacity of the brain, accumulation of acetaldehyde, and ethanol-induced hypnosis in animals in vivo. METHODS: Randomly outbred albino rats were treated with ethanol, and the duration of ethanol-induced loss of the righting response (sleep time) was measured. They were killed 2 weeks later (without further in vivo administration of ethanol), and brain homogenates were prepared to measure the accumulation of acetaldehyde from ethanol added in vitro. In a similar way, we determined the sleep time and, 5 days later, the rates of acetaldehyde accumulation in brains of heterogeneous mice. RESULTS: Significant correlations between the duration of ethanol-induced sleep and acetaldehyde accumulation in vitro were found. The Km value of the process of acetaldehyde accumulation was lower in long-sleeping, as compared with short-sleeping, rats. A similar result was also obtained in genetically heterogeneous mice. Animals with a longer duration of ethanol-induced sleep had a higher level of the accumulation of ethanol-derived acetaldehyde in brain homogenates, as compared with the short-sleeping mice. Rats and mice with the intermediate duration of ethanol-induced sleep had an intermediate value of acetaldehyde accumulation in brain homogenates. There was no correlation between brain catalase activity and ethanol-induced loss of the righting response in either the rats or the mice. CONCLUSIONS: This study is a direct demonstration of the positive correlation between ethanol-derived acetaldehyde accumulation in vitro in the brain and a central (behavioral) effect of alcohol in outbred rats and mice in vivo.
Assuntos
Encéfalo/metabolismo , Depressores do Sistema Nervoso Central/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Etanol/metabolismo , Etanol/farmacologia , Hipnóticos e Sedativos/farmacologia , Acetaldeído/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Catalase/metabolismo , Cinética , Masculino , Ratos , Sono/efeitos dos fármacos , Sono/genética , Fatores de TempoRESUMO
BACKGROUND: To clarify the role of brain acetaldehyde in the hypnotic effect of ethanol, we compared the ethanol-oxidizing capacity (rate of acetaldehyde accumulation) and catalase and aldehyde dehydrogenase activity in the brains of animals genetically selected for different sensitivities to the hypnotic effect of ethanol. METHODS: We used high, low, or control alcohol-sensitive rats (HAS, LAS, and CAS) and short- and long-sleep mice (SS and LS), as well as SS x LS recombinant inbred mice with known strain differences in mean duration of ethanol-induced sleep. We studied the rate of accumulation of acetaldehyde from ethanol in brain homogenates of these animals and correlated those values with their hypnotic sensitivity to ethanol. RESULTS: Acetaldehyde accumulation from ethanol was significantly higher in the brain homogenates from HAS rats and LS mice with high sensitivity to the hypnotic effect of ethanol in vivo, compared with LAS rats and SS mice with low sensitivity to ethanol. A correlation was found between the duration of ethanol-induced sleep and the in vitro rate of accumulation of ethanol-derived acetaldehyde in the brains of recombinant SS x LS mice strains. There was no correlation of sleep time with brain catalase levels. There were no line differences in brain catalase or aldehyde dehydrogenase or in alcohol or aldehyde dehydrogenase activity in livers of LAS, CAS, and HAS rats or in SS and LS mice. CONCLUSIONS: A correlation between the brain acetaldehyde accumulation, but not catalase levels, and the central effect of ethanol was demonstrated in animals genetically differing in initial sensitivity to the hypnotic effect of ethanol.
Assuntos
Encéfalo/metabolismo , Depressores do Sistema Nervoso Central/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Etanol/metabolismo , Etanol/farmacologia , Hipnóticos e Sedativos/farmacologia , Acetaldeído/metabolismo , Álcool Desidrogenase/metabolismo , Aldeído Desidrogenase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/enzimologia , Catalase/metabolismo , Cinética , Masculino , Camundongos , Ratos , Ratos Endogâmicos , Sono/efeitos dos fármacos , Sono/genética , Fatores de TempoRESUMO
A new method of fixation of native synaptosomes and synaptosomal membranes from rat striatum was applied for their visualization by atomic-force microscopy. A scheme for examination of the surface of biological material was developed, which helps to distinguish intact synaptosomes from washed synaptic membranes and evaluate damage to synaptic membrane surface caused by ethanol (25 mM) and acetaldehyde (50 microM). The proposed method can be used for evaluation of the damaging effects of ethanol and acetaldehyde on neurons.
Assuntos
Acetaldeído/farmacologia , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Terminações Nervosas/efeitos dos fármacos , Sinaptossomos/efeitos dos fármacos , Animais , Corpo Estriado/ultraestrutura , Microscopia de Força Atômica , Terminações Nervosas/ultraestrutura , Ratos , Sinaptossomos/ultraestruturaAssuntos
Acetaldeído/metabolismo , Comportamento Animal , Encéfalo/metabolismo , Etanol/metabolismo , Animais , Camundongos , Oxirredução , RatosRESUMO
It was found that the accumulation of acetaldehyde produced from 50 mM ethanol in rat brain homogenates takes place in all major brain regions. The velocity varied between 3.5 to 7.1 nmol/mg of protein/hr. The rate increased in the following order: brain hemispheres, striatum, brainstem, hypothalamus, and cerebellum. Significant regional differences in this process were found: in the initial period of incubation (5 min), acetaldehyde accumulation was maximal in the brain hemispheres; but, in the 30- to 60-min period, it became significantly higher in the cerebellum. Inhibition of this process by the catalase inhibitor, 3-amino-1,2,4-triazole (8 mM), was minimal in the brainstem (27%) and maximal (57%) in the cerebellum, despite nearly complete inhibition of catalase. This would indicate that processes other than catalase activity must contribute to acetaldehyde accumulation.
Assuntos
Encéfalo/enzimologia , Etanol/farmacocinética , Acetaldeído/metabolismo , Animais , Mapeamento Encefálico , Catalase/fisiologia , Cinética , Masculino , Ratos , Distribuição TecidualAssuntos
Desenvolvimento Embrionário e Fetal/efeitos dos fármacos , Etanol/toxicidade , Acetilcolinesterase/metabolismo , Administração por Inalação , Animais , Animais Recém-Nascidos , Corpo Estriado/metabolismo , Membrana Eritrocítica/efeitos dos fármacos , Membrana Eritrocítica/enzimologia , Etanol/administração & dosagem , Etanol/metabolismo , Feminino , Masculino , Lipídeos de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Gravidez , RatosRESUMO
Male rats were injected with ethanol as a 25% solution (3.5 g/kg body weight) and then the duration of the retention of the righting reflex (DRR) as well as the duration of ethanol-induced sleep (DEIS) were recorded. On the basis of DEIS in 60 rats, we selected four groups of six rats each: short-sleep group (SS, 34 +/- 5 min), intermediate-sleep (IS, 118 +/- 3 min), long-sleep (LS, 186 +/- 5 min) and non-sleep rats (NS, 0 min). The striatal crude mitochondrial fraction was assayed for acetylcholinesterase activity (AChE, EC 3.1.1.7) and high-affinity choline uptake. NS rats manifested similarity of the above parameters to those determined in SS and IS rats. LS rats were distinguished by a higher AChE activity in comparison with NS animals.
Assuntos
Acetilcolinesterase/metabolismo , Intoxicação Alcoólica/fisiopatologia , Colina/metabolismo , Corpo Estriado/enzimologia , Fases do Sono/fisiologia , Acetilcolina/metabolismo , Animais , Técnicas de Cultura , Injeções Intraperitoneais , Masculino , Mitocôndrias/enzimologia , Equilíbrio Postural/fisiologia , RatosRESUMO
Albino male rats weighing 160-180 g were used to study the effect of short-term hypobaric hypoxia (ascent in an altitude chamber to 2500 m and 5000 m for 1 hr) on endogenous ethanol measured in blood, brain and liver; simultaneously enzymes responsible for ethanol and acetaldehyde metabolism were determined. Endogenous ethanol in blood and tissues was found to be a very sensitive marker of hypoxia which was not correlated with lactate, pyruvate, lipid peroxidation or 11-hydroxycorticosteroids. The latter parameters varied in response to severe hypoxia.
Assuntos
Encéfalo/metabolismo , Etanol/metabolismo , Hipóxia/metabolismo , Fígado/metabolismo , Oxigênio/administração & dosagem , Acetaldeído/metabolismo , Álcool Desidrogenase/metabolismo , Aldeído Desidrogenase/metabolismo , Animais , Câmaras de Exposição Atmosférica , Etanol/sangue , Hipóxia/sangue , Masculino , RatosRESUMO
Furazolidone, lithium carbonate, chlorprotixen and pyrroxan exert different effects on ethanol pharmacokinetics. Furazolidone decreases clearance of ethanol, increases its half-life with a simultaneous reduction of blood acetaldehyde concentration. Pyrroxan increases clearance and maximal concentration of ethanol. Chloprotixen effect is characterized by a concurrent increase of ethanol and acetaldehyde concentrations in the first hours after ethanol administration. Lithium carbonate produces no significant changes in ethanol pharmacokinetic parameters.