Chronic alcohol consumption and cerebral indices of oxidative stress: is there a link?
Alcohol Clin Exp Res
; 25(5): 717-25, 2001 May.
Article
en En
| MEDLINE
| ID: mdl-11371721
ABSTRACT
BACKGROUND:
It is still difficult to define the biochemical mechanisms that cause alterations in neuronal function and plasticity and neuronal cell loss in the brains of alcohol-dependent patients.METHODS:
To evaluate the extent of cerebral alcohol-induced oxidative stress ex vivo, we investigated the levels of glutathione (GSH), its oxidation product glutathione disulfide (GSSG, produced by GSH-peroxidases), and the activities of catalase and superoxide dismutases (SOD). In addition, selected brain regions from up to 22 subjects (versus controls) were studied post mortem to compare the amount of oxidized DNA-base 8-hydroxy-2'-deoxyguanosine (8-OHdG) with levels of deoxyguanosine (dG) in mitochondrial and nuclear DNA.RESULTS:
The most prominent findings showed significantly decreased GSH/(GSH+2GSSG) molar redox (oxidation-reduction) ratios in the corpus mamillare and cerebellum, which appeared due to an increase in GSSG caused by chronic alcohol intake. Catalase activity was increased in only the frontal cortex, whereas decreased catalase activity was found in the corpus callosum. In contrast, neither copper-zinc-superoxide dismutase (CuZnSOD) and manganese-superoxide dismutase (MnSOD) activities nor 8-OHdG/dG molar ratios were altered, although a tendency toward higher OHdG/dG ratios in temporal and parietal cortex from alcohol-dependent patients could be detected when mitochondrial DNA was analyzed selectively.CONCLUSIONS:
We propose that decreased brain GSH/(GSH+2GSSG) molar redox (oxidation-reduction) ratios in alcohol-dependent patients may reflect neural impairment due to increased peroxide production after chronic alcohol consumption. However, future experiments, investigating the activities of enzymes and cofactors involved in GSH synthesis and metabolism in the human brain, will have to validate the specificity of these results for oxidative stress.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
/
8_ODS3_consumo_sustancias_psicoactivas
Problema de salud:
2_sustancias_psicoativas
/
8_alcohol
Asunto principal:
Encéfalo
/
Estrés Oxidativo
/
Disulfuro de Glutatión
/
Desoxiguanosina
/
Alcoholismo
/
Glutatión
Tipo de estudio:
Prognostic_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Alcohol Clin Exp Res
Año:
2001
Tipo del documento:
Article
País de afiliación:
Alemania