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.
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.
Authors: Victor R Gordeuk; Sharmin F Diaz; Gladys O Onojobi; Ishmael Kasvosve; Zufan Debebe; Amanuel Edossa; Jeremy M Pantin; Shigang Xiong; Sergei Nekhai; Mehdi Nouraie; Hidekazu Tsukamoto; Robert E Taylor Journal: Alcohol Clin Exp Res Date: 2008-09-06 Impact factor: 3.455
Authors: Mariana Verdelho Machado; Paula Ravasco; Alexandra Martins; Maria Rosário Almeida; Maria Ermelinda Camilo; Helena Cortez-Pinto Journal: World J Gastroenterol Date: 2009-01-07 Impact factor: 5.742
Authors: Edyta Szurowska; Katarzyna Sikorska; E Izycka-Swieszewska; Tomasz Nowicki; Tomasz Romanowski; Krzysztof P Bielawski; Michał Studniarek Journal: BMC Gastroenterol Date: 2010-01-27 Impact factor: 3.067