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Hepcidin Bile

Khristy J Thompson, Jennifer Hein, Andrew Baez, Jose Carlo Sosa, Marianne Wessling-Resnick
Manganese (Mn) toxicity arises from nutritional problems, community and occupational exposures, and genetic risks. Mn blood levels are controlled by hepatobiliary clearance. The goals of this study were to determine the cellular distribution of Mn transporters in polarized hepatocytes, to establish an in vitro assay for hepatocyte Mn efflux, and to examine possible roles the Mn transporters would play in metal import and export. For these experiments, hepatocytoma WIF-B cells were grown for 12-14 days to achieve maximal polarity...
September 1, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
Chiara Raggi, Elena Gammella, Margherita Correnti, Paolo Buratti, Elisa Forti, Jesper B Andersen, Gianfranco Alpini, Shannon Glaser, Domenico Alvaro, Pietro Invernizzi, Gaetano Cairo, Stefania Recalcati
Cholangiocarcinoma (CCA) is a devastating liver tumour arising from malignant transformation of bile duct epithelial cells. Cancer stem cells (CSC) are a subset of tumour cells endowed with stem-like properties, which play a role in tumour initiation, recurrence and metastasis. In appropriate conditions, CSC form 3D spheres (SPH), which retain stem-like tumour-initiating features. Here, we found different expression of iron proteins indicating increased iron content, oxidative stress and higher expression of CSC markers in CCA-SPH compared to tumour cells growing as monolayers...
December 15, 2017: Scientific Reports
Chang Yeob Han, Ja Hyun Koo, Sung Hoon Kim, Sara Gardenghi, Stefano Rivella, Pavel Strnad, Se Jin Hwang, Sang Geon Kim
Hepatic stellate cell (HSC) activation on liver injury facilitates fibrosis. Hepatokines affecting HSCs are largely unknown. Here we show that hepcidin inhibits HSC activation and ameliorates liver fibrosis. We observe that hepcidin levels are inversely correlated with exacerbation of fibrosis in patients, and also confirm the relationship in animal models. Adenoviral delivery of hepcidin to mice attenuates liver fibrosis induced by CCl4 treatment or bile duct ligation. In cell-based assays, either hepcidin from hepatocytes or exogenous hepcidin suppresses HSC activation by inhibiting TGFβ1-mediated Smad3 phosphorylation via Akt...
December 22, 2016: Nature Communications
Jolana Cermanova, Zuzana Kadova, Eva Dolezelova, Marie Zagorova, Vaclav Safka, Milos Hroch, Tomas Laho, Magdalena Holeckova, Jaroslav Mokry, Petra Kovarikova, Jan Bures, Martin Sterba, Stanislav Micuda
The purpose of the present study was to compare the activity of two different clinically available iron chelators on the development of acute liver injury after administration of the bacterial endotoxin (lipopolysaccharide [LPS]) in rats. Lipopolysaccharide was administered either alone or after pretreatment with dexrazoxane (DEX) or deferoxamine (DFO). Control groups received only saline or its combination with either chelator. After 8 h, untreated LPS rats developed liver injury, with signs of inflammation and oxidative stress...
October 2014: Shock
Qiu-Ming Wang, Jian-Ling Du, Zhi-Jun Duan, Shi-Bin Guo, Xiao-Yu Sun, Zhen Liu
AIM: To investigate the effects of the heme oxygenase (HO)-1/carbon monoxide system on iron deposition and portal pressure in rats with hepatic fibrosis induced by bile duct ligation (BDL). METHODS: Male Sprague-Dawley rats were divided randomly into a Sham group, BDL group, Fe group, deferoxamine (DFX) group, zinc protoporphyrin (ZnPP) group and cobalt protoporphyrin (CoPP) group. The levels of HO-1 were detected using different methods. The serum carboxyhemoglobin (COHb), iron, and portal vein pressure (PVP) were also quantified...
May 21, 2013: World Journal of Gastroenterology: WJG
Ying-Hsien Huang, Ya-Ling Yang, Mao-Meng Tiao, Ho-Chang Kuo, Li-Tung Huang, Jiin-Haur Chuang
Obstructive jaundice (OJ) increases the risk of liver injury and sepsis, leading to increased mortality. Cholestatic liver injury is associated with a downregulation of hepcidin expression levels. In fact, hepcidin has an important antimicrobial effect, especially against Escherichia coli. It is unknown whether supplementing recombinant hepcidin is effective in alleviating cholestasis-induced liver injury and mortality in mice with superimposed sepsis. A mouse model of cholestasis was developed using extrahepatic bile duct ligation for 3 days...
June 2012: Peptides
Gabriela Kolouchova, Eva Brcakova, Petra Hirsova, Jolana Cermanova, Leos Fuksa, Jaroslav Mokry, Petr Nachtigal, Hana Lastuvkova, Stanislav Micuda
AIMS: To evaluate iron biochemistry and contributing liver mechanisms during obstructive cholestasis and pravastatin treatment in rats. MAIN METHODS: A rat model of cholestasis induced by bile duct ligation (BDL) was used for the study. The detection of iron and the expression of relevant molecules were performed one week after surgery in the control, and cholestatic animals after treatment with either saline or pravastatin (1mg/kg/day). KEY FINDINGS: Saline-administered BDL rats showed, in comparison to sham-operated animals, a significant increase in plasma iron concentration, increased liver protein content of heme oxygenase-1 (HO-1) and a decline in the expression of hepcidin...
November 7, 2011: Life Sciences
Pavel Strnad, Peggy Schwarz, Maria C D Rasenack, Ozlem Kucukoglu, Rayan I Habib, Dominik Heuberger, Robert Ehehalt, Michael W Müller, Adolf Stiehl, Guido Adler, Hasan Kulaksiz
BACKGROUND/AIMS: Hepcidin (gene name HAMP), an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections...
January 24, 2011: PloS One
Jayantha Arnold, Arvind Sangwaiya, Vijay Manglam, Frank Geoghegan, Mark Thursz, Mark Busbridge
AIM: To examine body fluids such as ascitic fluid (AF), saliva, bile and pleural effusions for the presence of hepcidin using a novel radioimmunoassay (RIA). METHODS: Serum samples were collected from 25 healthy volunteers (mean age: 36 +/- 11.9 years, 11 males, 14 females). In addition bile was obtained from 12 patients undergoing endoscopic retrograde cholangiopancreatography (mean age: 66.9 +/- 16.7 years, M:F = 5:7). Saliva was collected from 17 healthy volunteers (mean age: 35 +/- 9...
May 7, 2010: World Journal of Gastroenterology: WJG
E Bilbao, D Raingeard, O Diaz de Cerio, M Ortiz-Zarragoitia, P Ruiz, U Izagirre, A Orbea, I Marigómez, M P Cajaraville, I Cancio
Thicklip grey mullets Chelon labrosus inhabit coastal and estuarine areas where they can be chronically exposed to commonly released pollutants such as polycyclic aromatic hydrocarbons (PAHs) and perfluorinated compounds. These pollutants can also originate from accidental spills, such as the Prestige oil spill in 2002, which resulted in the release of a heavy fuel oil that affected coastal ecosystems in the Bay of Biscay. Peroxisome proliferation (PP), induced biotransformation metabolism, immunosuppression and endocrine disruption are some of the possible biological effects caused by such chemicals...
July 1, 2010: Aquatic Toxicology
Ying-Hsien Huang, Jiin-Haur Chuang, Ya-Ling Yang, Chao-Cheng Huang, Chia-Ling Wu, Chao-Long Chen
Hepcidin is downregulated during progressive cholestasis in biliary atresia, but the mechanism is unknown. To verify whether downregulation of hepcidin is specific to cholestasis irrespective of the patient's age, we first analyzed liver hepcidin mRNA and protein expression in adults with primary biliary cirrhosis (PBC) (n=4), non-cholestatic cirrhosis (n=19) and in controls (n=9). We evaluated the tyrosine phosphorylation of signal transducer and activator of transcription 3 (pSTAT3) expressions in the liver sections...
October 2009: Laboratory Investigation; a Journal of Technical Methods and Pathology
Torsten Wuestefeld, Christian Klein, Konrad L Streetz, Naiara Beraza, Jürgen Schölmerich, Lawrence J Burgart, Lars Zender, Stefan Kubicka, Edwina Baskin-Bey, Gregory J Gores, Michael P Manns, Christian Trautwein
Chronic cholestasis is associated with increased bacterial infections and sepsis resulting in higher mortality in humans. In the current study, we investigated the relevance of gp130-dependent pathways after bile duct ligation (BDL). BDL was performed in conditional gp130 knockout (loxP/Cre system) mice and respective controls. Liver injury, regulation of the acute phase response, and the impact on survival and bacterial infections were determined. Acute BDL resulted in increased IL-6 levels, Stat3 activation, and an increase in acute-phase proteins (serum-amyloid-A [SAA]), which was blocked in gp130-deleted animals...
November 2005: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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