title: Chronic alcohol consumption and cerebral indices of oxidative stress: is there a link?
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.
authors.affiliation: Departments of Psychiatry, Pharmacology and Toxicology, University of Würzburg, Germany. mario.goetz@mail.uni-wuerzburg.de
authors.forename: M E
authors.initials: ME
authors.lastname: Götz
authors.forename: B
authors.initials: B
authors.lastname: Janetzky
authors.forename: S
authors.initials: S
authors.lastname: Pohli
authors.forename: A
authors.initials: A
authors.lastname: Gottschalk
authors.forename: W
authors.initials: W
authors.lastname: Gsell
authors.forename: T
authors.initials: T
authors.lastname: Tatschner
authors.forename: G
authors.initials: G
authors.lastname: Ransmayr
authors.forename: F
authors.initials: F
authors.lastname: Leblhuber
authors.forename: M
authors.initials: M
authors.lastname: Gerlach
authors.forename: H
authors.initials: H
authors.lastname: Reichmann
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: J
authors.initials: J
authors.lastname: Böning
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002374:Catalase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D005978:Glutathione; D019803:Glutathione Disulfide