Copper is one of the major metals causing environmental contamination. Previous studies showed that copper induced toxic effects in isolated perfused rat liver models and these effects were associated with lipid peroxidation. Here we investigated whether effects of copper (at concentrations of 0.01, 0.03, and 0.1 mM of Cu(2+) in Krebs-Henseleit buffer perfusing the isolated rat liver for 60 min), were associated with biliary epithelial cell injury, as well as protein oxidation and oxidative DNA damage. The highest concentration of copper in perfusate (0.1 mM) did not allow complete evaluation of all parameters because it blocked portal flow within 30 min of perfusion, indicating severe microcirculatory disturbances. Further, copper decreased secretion of bile and it increased lactate dehydrogenase, aspartate transaminase, and alanine transaminase leakage into perfusate as well as liver weight in a dose-dependent manner. Biliary gamma-glutamyltransferase, an index of biliary epithelial cell integrity increased similarly at 0.01 and 0.03 mM copper concentrations in perfusate. Compared to controls, 0.01 and 0.03 mM concentrations of copper increased the amount of thiobarbituric acid reacting substances, a marker of lipid peroxidation, tissue protein carbonyl groups, an index of protein oxidation, and 8-oxo-7,8-dihydro-2'-deoxyguanosine, a marker of oxidative DNA damage. The results suggest that toxic effects of copper in the isolated perfused rat liver may involve biliary epithelial cells and they are associated with lipid peroxidation, protein oxidation, and oxidative DNA damage.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.etp.2006.09.001 | DOI Listing |
EMBO Rep
January 2025
Division of Signal Transduction and Growth Control, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Heidelberg, Germany.
Ductular reaction (DR) is the hallmark of cholestatic diseases manifested in the proliferation of bile ductules lined by biliary epithelial cells (BECs). It is commonly associated with an increased risk of fibrosis and liver failure. The receptor for advanced glycation end products (RAGE) was identified as a critical mediator of DR during chronic injury.
View Article and Find Full Text PDFAm J Pathol
December 2024
Department of Microbiology and Immunology, Virginia Commonwealth University and Richmond VA Medical Center, Richmond, Virginia; Stravitz-Sanyal Institute for Liver Disease and Metabolic Health, School of Medicine, Virginia Commonwealth University, Richmond, Virginia. Electronic address:
Cholangiocarcinoma (CCA) is a rare but highly malignant carcinoma of bile duct epithelial cells with a poor prognosis. The major risk factors of CCA carcinogenesis and progression are cholestatic liver diseases. The key feature of primary sclerosing cholangitis and primary biliary cholangitis is chronic cholestasis, which means a slowdown of hepatocyte secretion of biliary lipids and metabolites into bile as well as a slowdown of enterohepatic circulation (bile acid recirculation) of bile acids with dysbiosis of the gut microbiome, which was shown to lead to enterohepatic recirculation and an increase of toxic secondary bile acids.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Department of Thoracic Surgery Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
Objective: Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal hepatobiliary malignancy with an increasing incidence annually. Extensive research has elucidated the existence of a reciprocal interaction between platelets and cancer cells, which promotes tumor proliferation and metastasis. This study aims to investigate the function and mechanism underlying iCCA progression driven by the interplay between platelets and tumor cells, aiming to provide novel therapeutic strategies for iCCA.
View Article and Find Full Text PDFWorld J Gastroenterol
December 2024
Department of Surgery, Chungnam National University Hospital, Daejeon 35015, South Korea.
Background: Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver.
View Article and Find Full Text PDFClin Res Hepatol Gastroenterol
December 2024
Department of Pathology, Fukui Saiseikai Hospital, Fukui 918-8503, Japan.
Background & Aims: Biliary epithelial senescence is involved in the pathogenesis of primary biliary cholangitis (PBC). We hypothesized that a unique subtype of programmed death-ligand 1 (PD-L1)-positive senescent biliary epithelial cells (BECs) may be related to the pathogenesis of PBC in association with cyclic GMP-AMP synthase (cGAS)- stimulator of interferon genes (STING) pathway.
Approach & Results: The expression of PD-L1, STING and their association with senescent markers p16 and p21 were immunohistochemically determined in livers taken from the patients with PBC (n = 87) and 97 diseased and normal control livers.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!