Up-regulation of transferrin receptor expression in hepatocytes by habitual alcohol drinking is implicated in hepatic iron overload in alcoholic liver disease.
BACKGROUND
Hepatic iron overload is often seen in alcoholic liver disease (ALD). We previously reported that the expression of 4-hydroxy-2-nonenal-protein adducts, which is a lipid peroxidative product and can be used as a marker of radical-mediated cellular damage, was increased in iron-overloaded hepatocytes with ALD. However, the mechanism of hepatic iron overload in ALD has not been clarified. In this study, to elucidate the mechanism of hepatic iron overload in ALD, we immunohistochemically investigated the expression of transferrin receptor (TfR), which mainly acts for cellular iron uptake.


METHODS
Hepatic tissues were obtained from 31 patients with ALD and 5 normal livers by percutaneous needle biopsy under laparoscopy or ultrasound guidance. Chemical detection of hepatic iron accumulation was performed by Perls' Prussian blue stain. Immunohistochemical detection of TfR expression was done using human monoclonal anti-TfR antibody (TR104) according to the avidin-biotin complex method with alkaline phosphatase.


RESULTS
Excess iron accumulation was found in 22 hepatic tissues with ALD but not in any normal hepatic tissues. TfR expression was increased in hepatocytes of 18 hepatic tissues with ALD but was not detected in any normal hepatic tissues. The mean duration of abstinence of patients who demonstrated positive TfR expression in hepatocytes was significantly shorter than that of patients who demonstrated negative TfR expression (positive: 14 days; negative: 30 days). However, total ethanol consumption, daily ethanol intake, and serum aspartate aminotransferase and gamma-glutamyl transpeptidase values on admission were not significantly correlated with TfR expression in hepatocytes.


CONCLUSIONS
The up-regulation of TfR expression in hepatocytes is implicated in hepatic iron overload in ALD, and habitual alcohol drinking is an important factor for the induction of TfR expression.
Suzuki
Yasuaki
Y
Third Medical Department of Internal Medicine, Asahikawa Medical College, Midorigoaka-Higashi, Japan.
Saito
Hiroyuki
H
Suzuki
Masako
M
Hosoki
Yayoi
Y
Sakurai
Shinobu
S
Fujimoto
Yoshinori
Y
Kohgo
Yutaka
Y
D000437:Alcoholism / Q000473:pathology*; D001707:Biopsy, Needle; D022781:Hepatocytes / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D019190:Iron Overload / Q000473:pathology*; D015227:Lipid Peroxidation / Q000502:physiology; D008099:Liver / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology*; D008111:Liver Function Tests; D011990:Receptors, Transferrin / Q000378:metabolism*; D012016:Reference Values; D015854:Up-Regulation / Q000502:physiology
D011990:Receptors, Transferrin