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Hepatic iron

Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Lola Corzo, Susana Rodríguez, Ramón Alejo, Lucía Fernández-Novoa, Gjumrakch Aliev, Ramón Cacabelos
Menopause is a natural event in women´s lives leading to the cessation of menstruation and the reproductive function due to loss of the ovarian follicular function. Menopause-derived estrogen deprivation and related endocrine factors are linked to some symptoms of middle-aged women, such as hot flashes, aches, joint pain, stiffness, depressed mood, bone degeneration, nutritional dysfunction, or difficulty to maintain body mass. Clinical approaches to these problems often involve hormone replacement therapy (HRT) and other modalities of therapeutic intervention...
October 14, 2016: Current Drug Metabolism
Ralf B Loeffler, M Beth McCarville, Anne W Wagstaff, Matthew P Smeltzer, Axel J Krafft, Ruitian Song, Jane S Hankins, Claudia M Hillenbrand
BACKGROUND: Liver R2* values calculated from multi-gradient echo (mGRE) magnetic resonance images (MRI) are strongly correlated with hepatic iron concentration (HIC) as shown in several independently derived biopsy calibration studies. These calibrations were established for axial single-slice breath-hold imaging at the location of the portal vein. Scanning in multi-slice mode makes the exam more efficient, since whole-liver coverage can be achieved with two breath-holds and the optimal slice can be selected afterward...
October 17, 2016: Pediatric Radiology
Y Cedeño, M López-Alonso, M Miranda
OBJECTIVES: Defects in copper metabolism have been described in several dog breeds, and recently, it has been suggested that changes in other essential trace elements could be involved in the pathogenesis of hepatic disease. This study measured hepatic copper accumulation and its interactions with other essential trace and toxic metals in dogs diagnosed with chronic hepatitis. METHODS: Liver samples of 20 chronic hepatitis and 20 healthy dogs were collected. Samples were acid digested, and essential metals (cobalt, copper, iron, manganese, molibdenum, selenium and zinc) and toxic metals (arsenic, cadmium, mercury and lead) were analysed by inductively-coupled plasma mass spectrometry...
October 16, 2016: Journal of Small Animal Practice
José María Moreno-Navarrete, María Moreno, Josep Puig, Gerard Blasco, Francisco Ortega, Gemma Xifra, Wifredo Ricart, José Manuel Fernández-Real
BACKGROUND & AIMS: Serum hepcidin concentration is known to increase in parallel to circulating markers of iron stores. We aimed to investigate whether this is reflected at the tissue level in subjects with obesity. METHODS: Serum hepcidin and ferritin levels (ELISA) and hepatic iron content (using magnetic resonance imaging) were analyzed longitudinally in 44 participants (19 without obesity and 25 with obesity). In a subgroup of 16 participants with obesity, a weight loss intervention was performed...
September 29, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Anastasia Asimakopoulou, Sabine Weiskirchen, Ralf Weiskirchen
Lipocalin 2 (LCN2) is a secreted protein that belongs to the Lipocalins, a group of transporters of small lipophilic molecules such as steroids, lipopolysaccharides, iron, and fatty acids in circulation. Two decades after its discovery and after a high variety of published findings, LCN2's altered expression has been assigned to critical roles in several pathological organ conditions, including liver injury and steatosis, renal damage, brain injury, cardiomyopathies, muscle-skeletal disorders, lung infection, and cancer in several organs...
2016: Frontiers in Physiology
Kensuke Usuki
Treatments of aplastic anemia are comprised of supportive therapy and aplastic anemia-specific therapy aimed at restoring hematopoiesis. Supportive therapies include transfusion, G-CSF, and the administration of iron chelation agents, as well as dealing specifically with individual symptoms. Aplastic anemia-specific treatments given with the aim of achieving hematopoietic recovery include immunosuppressive therapy, allogeneic hematopoietic stem cell transplantation, and anabolic hormone therapy. Although transplantation provides complete recovery of hematopoiesis (cure), there is a risk of death due to transplant-related complications...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
Michela Asperti, Tanja Stuemler, Maura Poli, Magdalena Gryzik, Lena Lifshitz, Esther G Meyron-Holtz, Israel Vlodavsky, Paolo Arosio
Hepcidin is the key regulator of systemic iron availability that acts by controlling the degradation of the iron exporter ferroportin. It is expressed mainly in the liver and regulated by iron, inflammation, erythropoiesis and hypoxia. The various agents that control its expression act mainly via the BMP6/SMAD signaling pathway. Among them are exogenous heparins, which are strong hepcidin repressors with a mechanism of action not fully understood but that may involve the competition with the structurally similar endogenous Heparan Sulfates (HS)...
2016: PloS One
Jing Wang, Ailian Dong, Gang Liu, Gregory J Anderson, Tony Y Hu, Jian Shi, Yulin Hu, Guangjun Nie
Chronic hepatitis B virus (HBV) infection often develop into cirrhosis, and both are major risk factors of hepatocellular carcinoma. However, effective approaches for the monitoring of HBV-related disease progress are still in need. Increased iron storage has an important role in HBV-related diseases. Hepcidin is a key regulator of iron homeostasis whose expression changes are often indicative of abnormal iron metabolism. There are few reports of hepcidin levels in patients with HBV infections, and the available results are inconsistent...
October 3, 2016: Scientific Reports
Laurence J Britton, V Nathan Subramaniam, Darrell Hg Crawford
The mechanisms that promote liver injury in non-alcoholic fatty liver disease (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models...
September 28, 2016: World Journal of Gastroenterology: WJG
Marta B Afonso, Pedro M Rodrigues, André L Simão, Dimitry Ofengeim, Tânia Carvalho, Joana D Amaral, Maria M Gaspar, Helena Cortez-Pinto, Rui E Castro, Junying Yuan, Cecília M P Rodrigues
Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangitis (PBC) patients and in wild-type and RIP3-deficient (RIP3(-/-)) mice subjected to common bile duct ligation (BDL)...
2016: Cell Death & Disease
Fabrice Lainé, Marc Ruivard, Véronique Loustaud-Ratti, Fabrice Bonnet, Paul Calès, Edouard Bardou-Jacquet, Sylvie Sacher-Huvelin, Xavier Causse, Christine Beusnel, Alain Renault, Eric Bellissant, Yves Deugnier
: Dysmetabolic iron overload syndrome (DIOS) is a common cause of hyperferritinaemia accounting for mild increase of iron stores in insulin-resistant subjects. Iron removal could improve insulin sensitivity. We performed a prospective, randomized, controlled trial (NCT01015525) in nondiabetic DIOS patients with hepatic iron >50µmol/g at MRI to compare the metabolic and hepatic outcomes of one-year maintenance of serum ferritin levels <50µg/l by bloodletting associated with lifestyle and diet advice (LFDA) to those of LFDA only...
September 29, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Kosha Mehta, Mark Busbridge, Derek Renshaw, Robert W Evans, Sebastien Farnaud, Vinood B Patel
Hepcidin is the key regulator of systemic iron homeostasis. The iron-sensing mechanisms and the role of intracellular iron in modulating hepatic hepcidin secretion are unclear. Therefore, we created a novel cell line, recombinant-TfR1 HepG2, expressing iron-response-element-independent TFRC mRNA to promote cellular iron-overload and examined the effect of excess holotransferrin (5g/L) on cell-surface TfR1, iron content, hepcidin secretion and mRNA expressions of TFRC, HAMP, SLC40A1, HFE and TFR2. Results showed that the recombinant cells exceeded levels of cell-surface TfR1 in wild-type cells under basal (2...
October 2016: Blood Cells, Molecules & Diseases
George Petrakos, Panagiotis Andriopoulos, Maria Tsironi
Advances in treatment of thalassemia have led to the aging of thalassemic patients, and consequently concern about successful reproductive outcome is augmented. Although women with thalassemia intermedia only were considered competent of achieving pregnancy, case series reveal the willingness of both thalassemia major and thalassemia intermedia women to have a family. Pregnancy in general is characterized by dynamic multiple-system changes and increased susceptibility to oxidative stress, while homozygous, transfusion-dependent, β-thalassemia patients manifest cardiac, hepatic, endocrine, and metabolic disorders attributable to chronic anoxia and iron overload and thalassemia intermedia, usually nontransfused, is associated with augmented risk of thromboembolic events...
2016: International Journal of Women's Health
Wencai Shi, Heyang Wang, Xuan Zheng, Xin Jiang, Zheng Xu, Hui Shen, Min Li
Hepcidin synthesis is reported to be inadequate according to the body iron store in patients with non-alcoholic fatty liver disease (NAFLD) undergoing hepatic iron overload (HIO). However, the underlying mechanisms remain unclear. We hypothesize that hepatocyte nuclear factor-4α (HNF-4α) may negatively regulate hepcidin expression and contribute to hepcidin deficiency in NAFLD patients. The effect of HNF-4α on hepcidin expression was observed by transfecting specific HNF-4α small interfering RNA (siRNA) or plasmids into HepG2 cells...
September 23, 2016: Biological Trace Element Research
Nirav Pipaliya, Dattatray Solanke, Pathik Parikh, Meghraj Ingle, Ratna Sharma, Sujata Sharma, Prabha Sawant
BACKGROUND & AIMS: We investigated whether tissue elastography (TE) can be used as an alternative to magnetic resonance imaging (MRI) T2* analysis to determine the degree of iron overload in patients with thalassemia major. METHODS: We conducted a prospective study 154 patients (99 male; mean age, 12±3.6 years) with thalassemia major requiring chronic blood transfusion and on iron chelator therapy. The study was performed at a tertiary hospital in India from January 2015 through June 2015...
September 17, 2016: Clinical Gastroenterology and Hepatology
Minjun Wang, Wenbo Tang, Hong Xin, Yi Zhun Zhu
Anemia of inflammation (AI) is clinically prevalent and greatly threatens public health. Traditional remedies have raised controversy during clinical practice, calling for alternative therapies. We have recently found that hydrogen sulfide (H2S) inhibits inflammatory hepcidin, the critical mediator of AI. However, due to the chemical property of H2S, there remains an urgent need for a stable H2S donor in AI treatment. Here we reported that S-propargyl-cysteine (SPRC), a novel water-soluble H2S donor, suppressed hepatic hepcidin and corrected hypoferremia induced by lipopolysaccharide...
2016: PloS One
Yang Qiao, Huan He, Zeyu Zhang, Zhangping Liao, Dong Yin, Dan Liu, Bo Yi, Ming He
Ferulic acid is a polyphenolic compound contained in various types of fruits and wheat bran. As a salt of the active ingredient, sodium ferulate (SF) has potent free radical scavenging activity and can effectively scavenge ROS. In this study, we examined the effect of SF on iron-overloaded mice in comparison to a standard antioxidant, taurine (TAU). We determined the protective role of SF against liver injury by examining liver-to-body ratio (%), transaminase and hepatocyte apoptosis in rats supplied with 10% dextrose intraperitoneal injection...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Judit Pomothy, Gergely Szombath, Patrik Rokonál, Gábor Mátis, Zsuzsanna Neogrády, Torsten Steinmetzer, Erzsébet Pászti-Gere
Purpose. Dysfunction of matriptase-2 can be involved in iron regulatory disorder via downregulation of hepcidin expression. In the present study, we investigated the effects of 3-amidinophenylalanine-derived matriptase inhibitors on porcine hepatic inflammatory cell models. Methods. Hepatocyte-Kupffer cell cocultures (ratio of 2 : 1 and 6 : 1) were treated with four structurally related matriptase inhibitors at 50 μM. Cell cytotoxicity and relative expressions of IL-6 and IL-8 and the levels of hepcidin were determined by MTS and porcine-specific ELISA...
2016: BioMed Research International
Hak Chung, Dayong Wu, Donald Smith, Simin Nikbin Meydani, Sung Nim Han
High-fat diet (HFD)-induced obesity has been reported to result in low hepatic iron storage. In the current study, we tested the hypothesis that these obesity-related changes in hepatic iron status could be reversed by decreasing adiposity by feeding a low-fat diet. Five-week-old C57BL/6 mice were assigned to 3 groups: the LL group was fed a control diet for 31 weeks, the HH group was fed a HFD for 31 weeks, and the HL group was fed the HFD for 15 weeks and then switched to the control diet for 16 weeks. The fat mass of the HL group decreased by 3...
September 2016: Nutrition Research
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