title: Covalent protein adducts in the liver as a result of ethanol metabolism and lipid peroxidation.
abstract: BACKGROUND
  The primary mechanisms of ethanol-induced tissue damage have been suggested to include aldehyde-derived protein modifications resulting from ethanol metabolism and lipid peroxidation. Conjugation of reactive aldehydes to a variety of target proteins and cellular constituents have been recently reported. This research was undertaken in order to examine the presence of covalent chemical addition products (adducts) of proteins and acetaldehyde, the first metabolite of ethanol, and those with malondialdehyde, a product of lipid peroxidation, as formed in vivo.
  
  
  METHODS
  Specific antibodies recognizing acetaldehyde- and malondialdehyde-modified epitopes in proteins were used in immunoperoxidase and double immunofluorescence stainings of liver specimens obtained from ethanol-fed rats and micropigs and from human alcoholics.
  
  
  RESULTS
  The centrilobular region of the liver contained the protein modifications both in alcohol-consuming humans and in animals fed ethanol before any apparent histologic damage. With inflammation and fibrosis, such protein modifications were more widespread, and the positive staining for the malondialdehyde-derived modification became more dominant. The presence of the adducts colocalized with the areas of fatty infiltration, focal necrosis and fibrosis. In addition, the erythrocytes of alcohol consumers were found to contain such modifications.
  
  
  CONCLUSIONS
  The studies support the view that covalent damage to proteins and cellular constituents induced by aldehyde-derived modifications in vivo may play a role in the sequence of events leading to liver disease in alcohol consumers. Species and dietary differences may be important in the relative contribution of lipid peroxidation to alcohol-induced tissue damage.
authors.affiliation: Department of Clinical Chemistry, Univeristy of Oulu, Finland.
authors.forename: O
authors.initials: O
authors.lastname: Niemelä
authors.forename: S
authors.initials: S
authors.lastname: Parkkila
authors.forename: S
authors.initials: S
authors.lastname: Ylä-Herttuala
authors.forename: C
authors.initials: C
authors.lastname: Halsted
authors.forename: J L
authors.initials: JL
authors.lastname: Witztum
authors.forename: A
authors.initials: A
authors.lastname: Lanca
authors.forename: Y
authors.initials: Y
authors.lastname: Israel
mesh_terms: D000079:Acetaldehyde / Q000737:chemistry; D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D006519:Hepatitis, Alcoholic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007158:Immunologic Techniques; D008054:Lipid Peroxides / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008315:Malondialdehyde / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D013556:Swine, Miniature
chemical_list: D008054:Lipid Peroxides; D011506:Proteins; D000431:Ethanol; D008315:Malondialdehyde; D000079:Acetaldehyde