Oxidative stress and an altered methionine metabolism in alcoholism.
The exact mechanism of brain atrophy in patients with chronic alcoholism remains unknown. There is growing evidence that chronic alcoholism is associated with oxidative stress and with a derangement in sulphur amino acid metabolism (e.g. ethanol-induced hyperhomocysteinemia). Furthermore, it has been reported that homocysteine induces neuronal cell death by stimulating N-methyl-D-aspartate receptors as well as by producing free radicals. To further evaluate this latter hypothesis we analysed serum levels of both homocysteine and markers of oxidative stress (malondialdehyde) in alcoholic patients who underwent withdrawal from alcohol. Homocysteine and malondialdehyde were quantified by high performance liquid chromatography (HPLC) in serum samples of 35 patients (active drinkers). There was a significant correlation (P<0. 01) between blood alcohol concentration and elevated homocysteine (Spearman's r=0.71) and malondialdehyde (r=0.90) levels on admission. In addition, homocysteine and malondialdehyde levels were found to be significant decreased after 3 days of withdrawal treatment (Wilcoxon test: homocysteine, Z=-5.127; malondialdehyde, Z=-3.120; P<0.01). We postulate that excitatory neurotransmitters and mechanisms of oxidative stress in patients with chronic alcoholism may partly mediate excitotoxic neuronal damage and hereby cause brain shrinkage.
Bleich
S
S
Department of Psychiatry, Georg-August-University, Von-Siebold-Strasse 5, D-37075, Göttingen, Germany. stefan.bleich@t-online.de
Spilker
K
K
Kurth
C
C
Degner
D
D
Quintela-Schneider
M
M
Javaheripour
K
K
Rüther
E
E
Kornhuber
J
J
Wiltfang
J
J
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D002719:Chlormethiazole / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D000431:Ethanol / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008715:Methionine / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress
D006993:Hypnotics and Sedatives; D002719:Chlormethiazole; D006710:Homocysteine; D000431:Ethanol; D008315:Malondialdehyde; D008715:Methionine