title: S-adenosylmethionine decreases the peak blood alcohol levels 3 h after an acute bolus of ethanol by inducing alcohol metabolizing enzymes in the liver.
abstract: BACKGROUND
  An alcohol bolus causes the blood alcohol level (BAL) to peak at 1-2 h post ingestion. The ethanol elimination rate is regulated by alcohol metabolizing enzymes, primarily alcohol dehydrogenase (ADH1), acetaldehyde dehydrogenase (ALDH), and cytochrome P450 (CYP2E1). Recently, S-adenosylmethionine (SAMe) was found to reduce acute BALs 3 h after an alcohol bolus. The question, then, was: what is the mechanism involved in this reduction of BAL by feeding SAMe? To answer this question, we investigated the changes in ethanol metabolizing enzymes and the epigenetic changes that regulate the expression of these enzymes during acute binge drinking and chronic drinking.
  
  
  METHODS
  Rats were fed a bolus of ethanol with or without SAMe, and were sacrificed at 3 h or 12 h after the bolus.
  
  
  RESULTS
  RT-PCR and Western blot analyses showed that SAMe significantly induced ADH1 levels in the 3 h liver samples. However, SAMe did not affect the changes in ADH1 protein levels 12 h post bolus. Since SAMe is a methyl donor, it was postulated that the ADH1 gene expression up regulation at 3 h was due to a histone modification induced by methylation from methyl transferases. Dimethylated histone 3 lysine 4 (H3K4me2), a modification responsible for gene expression activation, was found to be significantly increased by SAMe at 3 h post bolus.
  
  
  CONCLUSIONS
  These results correlated with the low BAL found at 3 h post bolus, and support the concept that SAMe increased the gene expression to increase the elimination rate of ethanol in binge drinking by increasing H3K4me2.
authors.affiliation: Department of Pathology, LABioMed Harbor-UCLA Medical Center, Torrance, CA 90509, USA.
authors.forename: Fawzia
authors.initials: F
authors.lastname: Bardag-Gorce
authors.forename: Joan
authors.initials: J
authors.lastname: Oliva
authors.forename: Wesley
authors.initials: W
authors.lastname: Wong
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fong
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Barbara A
authors.initials: BA
authors.lastname: French
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
mesh_terms: D000426:Alcohol Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D019175:DNA Methylation / Q000187:drug effects; D000431:Ethanol / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects*; D006657:Histones / Q000187:drug effects / Q000378:metabolism; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012436:S-Adenosylmethionine / Q000494:pharmacology*
chemical_list: D006657:Histones; D000431:Ethanol; D012436:S-Adenosylmethionine; D000426:Alcohol Dehydrogenase