Hepatic lipid peroxidation in hereditary hemochromatosis and alcoholic liver injury

Studies in experimental animals have indicated that enhanced lipid peroxida tion 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 for mation of lipid peroxidation-derived aldehydes in the liver of patients wit h hereditary hemochromatosis (HH) and alcohol abuse. Liver biopsy specimens from 10 nondrinking patients with HH were evaluated. These patients were c lassified as having HH based on hepatic iron index or human leukocyte antig en identity with a known proband, All patients were homozygous for the Cys2 82Tyr mutation. In addition, 8 patients with alcoholic liver disease were e xamined, 2 of whom also had hemochromatosis, For comparison, 17 patients wi th liver diseases unrelated to iron overload or alcohol abuse were studied. Liver biopsy specimens were immunostained for protein adducts with malondi aldehyde and 4-hydroxynonenal, Both malondialdehyde- and 4-hydroxynonenal-p rotein adducts were found from liver specimens of patients with HH and alco hol abuse in more abundant amounts than from patients in a control group. I n alcoholics the adducts were primarily in zone 3, whereas in hemochromatos is staining had an acinar zone 1 predominance, which followed the localizat ion of iron. The most abundant amounts of protein adducts were noted in pat ients with alcohol abuse plus iron overload. The data support the concept t hat both chronic alcohol use and iron overload induce hepatic lipid peroxid ation. Through formation of reactive aldehydic products, excessive alcohol consumption and iron overload may have additive hepatotoxic effects.