Immunohistochemical detection of 4-hydroxy-2-nonenal-modified-protein adducts in human alcoholic liver diseases.
4-Hydroxy-2-nonenal (HNE) is one of the major components of lipid peroxidation product and has been shown to react with proteins to form HNE-protein adducts. HNE-protein adducts are relatively stable and can be used as a marker of radical-mediated cellular damage. We report herein the immunohistochemical analysis of HNE-protein adducts in human alcoholic liver diseases using a specific monoclonal antibody HNEJ-2. Cytoplasm of hepatocytes and bile duct epithelia was positively stained for HNE-protein adducts, and the nucleus was negligibly stained. The immunohistochemical intensity of hepatocytes was classified into three groups: strong, moderate, and faint staining. Strong staining was found in 43% of alcoholic liver diseases and in 4% of viral liver diseases. Hepatocytes of alcoholic liver diseases contained a higher amount of HNE-protein adducts than those of viral liver diseases, and the difference was statistically significant (p = 0.005; chi2 test). Semiquantitative analysis of the histological intensities of HNE-protein adducts and iron indicated a significant positive correlation (p = 0.084; Spearman's rank correlation). The localization of HNE-protein adducts and iron in hepatocytes appeared to be identical. These data suggested the correlation between HNE-protein adducts and iron. Our results indicate that HNE-protein adducts, a marker of oxidative stress-induced damage, are increased in human alcoholic liver damage, and that hepatic siderosis may act on the production of free radicals.
Ohhira
M
M
Third Department of Internal Medicine, Asahikawa Medical College, Nishikagura, Japan.
Ohtake
T
T
Matsumoto
A
A
Saito
H
H
Ikuta
K
K
Fujimoto
Y
Y
Ono
M
M
Toyokuni
S
S
Kohgo
Y
Y
D000447:Aldehydes / Q000032:analysis*; D001707:Biopsy, Needle; D003432:Cross-Linking Reagents / Q000032:analysis*; D005609:Free Radicals; D006525:Hepatitis, Viral, Human / Q000473:pathology; D006801:Humans; D007501:Iron / Q000032:analysis; D015227:Lipid Peroxidation / Q000502:physiology*; D008099:Liver / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology*; D011506:Proteins / Q000032:analysis*
D000447:Aldehydes; D003432:Cross-Linking Reagents; D005609:Free Radicals; D011506:Proteins; D007501:Iron; C027576:4-hydroxy-2-nonenal