Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury.
Studies in experimental animals have indicated that enhanced lipid peroxidation may play a role in the hepatic injury produced by iron overload or by excessive alcohol consumption. The aim of this study was to compare the formation of lipid peroxidation-derived aldehydes in the liver of patients with hereditary hemochromatosis (HH) and alcohol abuse. Liver biopsy specimens from 10 nondrinking patients with HH were evaluated. These patients were classified as having HH based on hepatic iron index or human leukocyte antigen identity with a known proband. All patients were homozygous for the Cys282Tyr mutation. In addition, 8 patients with alcoholic liver disease were examined, 2 of whom also had hemochromatosis. For comparison, 17 patients with liver diseases unrelated to iron overload or alcohol abuse were studied. Liver biopsy specimens were immunostained for protein adducts with malondialdehyde and 4-hydroxynonenal. Both malondialdehyde- and 4-hydroxynonenal-protein adducts were found from liver specimens of patients with HH and alcohol abuse in more abundant amounts than from patients in a control group. In alcoholics the adducts were primarily in zone 3, whereas in hemochromatosis staining had an acinar zone 1 predominance, which followed the localization of iron. The most abundant amounts of protein adducts were noted in patients with alcohol abuse plus iron overload. The data support the concept that both chronic alcohol use and iron overload induce hepatic lipid peroxidation. Through formation of reactive aldehydic products, excessive alcohol consumption and iron overload may have additive hepatotoxic effects.
Niemelä
O
O
Department of Clinical Chemistry, University of Oulu, Finland.
Parkkila
S
S
Britton
R S
RS
Brunt
E
E
Janney
C
C
Bacon
B
B
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics; D000447:Aldehydes / Q000032:analysis; D005260:Female; D006680:HLA Antigens / Q000032:analysis; D006432:Hemochromatosis / Q000150:complications / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007501:Iron / Q000008:administration & dosage; D015227:Lipid Peroxidation / Q000235:genetics*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008875:Middle Aged; D009154:Mutation
D000447:Aldehydes; D006680:HLA Antigens; D008315:Malondialdehyde; D007501:Iron; C027576:4-hydroxy-2-nonenal