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Hepatic iron

Jung-Heun Ha, Caglar Doguer, Shireen R L Flores, Tao Wang, James F Collins
Background: Consumption of a high-iron diet causes copper deficiency in weanling rodents; however, the minimum amount of dietary iron that disrupts copper homeostasis has not been established. Objective: We tested the hypothesis that dietary iron at only several-fold above physiologic requirements would cause copper depletion. Methods: Weanling male Sprague-Dawley rats (n = 6/group) were fed AIN-93G-based diets with adequate (88 µg Fe/g = 1×), or excessive (4×, 9...
March 1, 2018: Journal of Nutrition
Sammy M Tabbah, Catalin S Buhimschi, Katherine Rodewald-Millen, Christopher R Pierson, Vineet Bhandari, Philip Samuels, Irina A Buhimschi
OBJECTIVE:  Hepcidin, a mediator of innate immunity, binds the iron exporter ferroportin, leading to functional hypoferremia through intracellular iron sequestration. We explored hepcidin-ferroportin interactions in neonates clinically diagnosed with early-onset neonatal sepsis (EONS). STUDY DESIGN:  Hepcidin and interleukin (IL)-6 were quantified by enzyme-linked immunosorbent assay (ELISA) in 92 paired cord blood-maternal blood samples in the following groups: "Yes" EONS ( n  = 41, gestational age [GA] 29 ± 1 weeks) and "No" EONS ( n  = 51, GA 26 ± 1 weeks)...
February 2, 2018: American Journal of Perinatology
Manon Viaud, Stoyan Ivanov, Nemanja Vujic, Madalina Duta-Mare, Lazaro-Emilio Aira, Thibault Barouillet, Elsa Garcia, François Orange, Isabelle Dugail, Isabelle Hainault, Christian Stehlik, Sandrine Marchetti, Laurent Boyer, Rodolphe Guinamard, Fabienne Foufelle, Andrea E Bochem, Kees G Hovingh, Edward B Thorp, Emmanuel L Gautier, Dagmar Kratky, Paul A Da Silva-Jardine, Laurent Yvan-Charvet
<u>Rationale:</u> Macrophages face a substantial amount of cholesterol following the ingestion of apoptotic cells and the lysosomal acid lipase (LIPA) has a major role in hydrolyzing cholesteryl esters in the endocytic compartment. <u>Objective:</u> Here, we directly investigated the role of LIPA-mediated clearance of apoptotic cells both in vitro and in vivo. <u>Methods and Results:</u> We show that LIPA inhibition causes a defective efferocytic response due to impaired generation of 25-OHC and 27-OHC...
March 9, 2018: Circulation Research
Gabriel Qualhato, Simone Maria Teixeira de Sabóia-Morais, Luciana Damacena Silva, Thiago Lopes Rocha
Although iron oxide nanoparticles (IONPs) have been widely used in nanomedicine and nanoremediation, their ecotoxicological effects on aquatic organisms remain unclear. In this study, the melanomacrophage center (MMC) response and hepatic histopathologic biomarkers were investigated in female guppies, Poecilia reticulata, exposed to citrate-functionalized IONPs (γ-Fe2 O3 ) at an environmentally relevant iron concentration (0.3 mg L-1 ) over 21 days. The animals were collected at the beginning of the experiment and after 3, 7, 14, and 21 days of exposure...
February 21, 2018: Aquatic Toxicology
Matthew R O'Connor, Michael M Garner
Within a 2-wk period, three African grey parrots ( Psittacus erithacus) presented for emergency treatment. All three parrots had depressed behavior, an inability to fly, and significant weight loss. Plasma chemistry abnormalities included severe hypoproteinemia and elevated liver enzymes in all parrots. Two of the parrots died, and histologic examination with hematoxylin and eosin and Prussian blue stains revealed severe hepatic iron storage. Quantitative analysis confirmed high hepatic iron concentrations...
March 2018: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Huimin Lin, Caixia Fu, Stephan Kannengiesser, Shu Cheng, Jun Shen, Haipeng Dong, Fuhua Yan
BACKGROUND: The coexistence of hepatic iron and fat is common in patients with hyperferritinemia, which plays an interactive and aggressive role in the progression of diseases (fibrosis, cirrhosis, and hepatocellular carcinomas). PURPOSE: To evaluate a modified high-speed T2 -corrected multi-echo, single voxel spectroscopy sequence (HISTOV) for liver iron concentration (LIC) quantification in patients with hyperferritinemia, with simultaneous fat fraction (FF) estimation...
March 7, 2018: Journal of Magnetic Resonance Imaging: JMRI
Paul J Schmidt, Kaifeng Liu, Gary Visner, Kevin Fitzgerald, Shannon Fishman, Tim Racie, Julia L Hettinger, James S Butler, Mark D Fleming
Diminished β-globin synthesis in β-thalassemia is associated with ineffective erythropoiesis, leading to secondary iron overload caused by inappropriately low levels of hepcidin and to splenomegaly in the symptomatic thalassemias. Splenectomy is often employed in patients with β-thalassemia in order to reduce hemolysis. Expression of the iron regulatory peptide hormone hepcidin is repressed by the serine protease TMPRSS6. Hepcidin induction by RNAi-mediated inhibition of TMPRSS6 expression reduces iron overload and mitigates anemia in murine models of β-thalassemia intermedia...
March 2, 2018: American Journal of Hematology
Hassan M Moukhadder, Joseph E Roumi, Rayan Bou-Fakhredin, Ali T Taher
The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is increasing, the two well recognized HCC risk factors in thalassemia being iron overload and chronic hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, whereas chronic hepatitis leads to necroinflammation that can accelerate progression to HCC. We hereby report the case of a non transfused, hepatitis C-negative, β-thalassemia intermedia (β-TI) patient from our practice who had evidence of significant iron overload, suggesting the importance of increased iron burden as a HCC risk factor in this patient population...
March 1, 2018: Hemoglobin
Elizabeth A Feldman, Christopher D Miller, Sarabeth Wojnowicz, Robert Seabury
Despite a boxed warning, postmarketing reports of deferasirox-associated hepatic injury in patients with chronic transfusions are not well described. Hepatic impairment, including failure, has been reported to occur more frequently in patients older than 55 years and in those with significant comorbidities, including liver cirrhosis and multiorgan failure. In this case report, we describe significant hyperbilirubinemia and acute hepatocellular jaundice related to deferasirox in a 7-year-old female being treated for iron overload secondary to chronic transfusions...
January 2018: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
Tolunay B Aydemir, Robert J Cousins
The SLC39A family of metal transporters was identified through homologies with the Zrt- and Irt-like (ZIP) proteins from yeast and plants. Of all the ZIP transporters, ZIP14 is arguably the most robustly characterized in terms of function at the integrative level. Mice with a global knockout of Zip14 are viable, thus providing the opportunity to conduct physiologic experiments. In mice, Zip14 expression is highly tissue specific, with the greatest abundance in the jejunum > liver > heart > kidney > white adipose tissue > skeletal muscle > spleen > pancreas...
February 1, 2018: Journal of Nutrition
Inka Gallitz, Niklas Lofruthe, Lisa Traeger, Nicole Bäumer, Verena Hoerr, Cornelius Faber, Tanja Kuhlmann, Carsten Müller-Tidow, Andrea U Steinbicker
BACKGROUND: Inflammatory stimuli induce the hepatic iron regulatory hormone hepcidin, which contributes to anaemia of inflammation (AI). Hepcidin expression is regulated by the bone morphogenetic protein (BMP) and the interleukin-6 (IL-6) signalling pathways. Prior results indicate that the BMP type I receptor ALK3 is mainly involved in the acute inflammatory hepcidin induction four and 72 h after IL-6 administration. In this study, the role of ALK3 in a chronic model of inflammation was investigated...
February 27, 2018: BMC Physiology
Victor Pereira, Paloma Carbajales, Marta López-Alonso, Marta Miranda
Animal feed has traditionally been supplemented with trace elements at dietary concentrations well above physiological needs. However, environmental concerns have led to calls for better adjustment of mineral supplementation to actual physiological needs and, in this context, consideration of breed-related differences in trace element requirements. The aim of this study was to analyze trace element concentrations in the main breeds used for intensive beef production in northern Spain (Holstein-Friesian [HF], Galician Blonde [GB], and GB × HF cross)...
February 24, 2018: Biological Trace Element Research
Mohammad Soleiman Soltanpour, Kambiz Davari
Objectives: Organ-specific hemosiderosis and iron overload complications are more serious and more frequent in some patients with beta thalassemia major (BTM) compared with others. We investigated whether coinheritance of HFE H63D or C282Y gene mutations in patients with BTM contributes to the phenotypic variation of iron overload complications and assessed the correlation of cardiac and hepatic hemosiderosis with plasma ferritin levels. Methods: We studied 60 patients with BTM with a mean age of 17...
January 2018: Oman Medical Journal
Yanyan Wei, Wei Ye, Wei Zhao
Background: Hepatocellular carcinoma (HCC) is common and the second leading causes of cancer-related deaths. HCC usually occurs on the basis of chronic liver diseases. At present, the study of iron metabolism in chronic liver diseases was limited to chronic HCV infection, nonalcoholic fatty liver disease, and alcoholic liver disease. This study aimed to investigate the effect of serum iron levels on the progression of chronic HBV infection and the relationship with the prognosis of HBV-related HCC. Methods: A respective study involving 277 healthy individuals as controls (HC), 295 patients with chronic hepatitis B (CHB), 224 patients with HBV-related liver cirrhosis (HBV-related LC), and 586 patients with HBV- related HCC were enrolled in this study...
2018: Frontiers in Physiology
Yuuki Yoshimura, Daisuke Suzuki, Kanae Miyahara
1 H-MRS, which is a method of measuring fat and iron deposits in the liver, has a single voxel spectroscopy imaging method called high-speed T2 -corrected multiecho (HISTO) based on the STEAM method. If HISTO measurement accuracy is high, it will be one of the biomarkers, so the measurement accuracy was examined. We imaged a self-made phantom simulating a known amount of fat and iron deposition in the liver. A regression analysis of HISTO-measured values for hepatic fat phantom was performed. In addition, regression analysis was performed on the hepatic iron phantom for the R2 values obtained from the T2 values measurement and the actually measured value of the HISTO...
2018: Nihon Hoshasen Gijutsu Gakkai Zasshi
Elisavet Stavropoulou, Gratiela G Pircalabioru, Eugenia Bezirtzoglou
Cytochromes are expressed in many different tissues of the human body. They are found mostly in intestinal and hepatic tissues. Cytochromes P450 (CYPs) are enzymes that oxidize substances using iron and are able to metabolize a large variety of xenobiotic substances. CYP enzymes are linked to a wide array of reactions including and O-dealkylation, S-oxidation, epoxidation, and hydroxylation. The activity of the typical P450 cytochrome is influenced by a variety of factors, such as genus, environment, disease state, herbicide, alcohol, and herbal medications...
2018: Frontiers in Immunology
Jay B Wish, George R Aronoff, Bruce R Bacon, Carlo Brugnara, Kai-Uwe Eckardt, Tomas Ganz, Iain C Macdougall, Julio Núñez, Adam J Perahia, John C Wood
BACKGROUND: Regulation of body iron occurs at cellular, tissue, and systemic levels. In healthy individuals, iron absorption and losses are minimal, creating a virtually closed system. In the setting of chronic kidney disease and hemodialysis (HD), increased iron losses, reduced iron absorption, and limited iron availability lead to iron deficiency. Intravenous (IV) iron therapy is frequently prescribed to replace lost iron, but determining an individual's iron balance and stores can be challenging and imprecise, contributing to uncertainty about the long-term safety of IV iron therapy...
February 13, 2018: American Journal of Nephrology
Ji Yun Jung, Sang Mi Park, Hae Li Ko, Jong Rok Lee, Chung A Park, Sung Hui Byun, Sae Kwang Ku, Il Je Cho, Sang Chan Kim
Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text]+[Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100μg/mL) significantly inhibited AA[Formula: see text]+[Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase...
February 12, 2018: American Journal of Chinese Medicine
Robert C Oh, Thomas R Hustead, Syed M Ali, Matthew W Pantsari
Mild, asymptomatic elevations (less than five times the upper limit of normal) of alanine transaminase and aspartate transaminase levels are common in primary care. It is estimated that approximately 10% of the U.S. population has elevated transaminase levels. An approach based on the prevalence of diseases that cause asymptomatic transaminase elevations can help clinicians efficiently identify common and serious liver disease. The most common causes of elevated transaminase levels are nonalcoholic fatty liver disease and alcoholic liver disease...
December 1, 2017: American Family Physician
Edina Pandur, Zsuzsanna Fekete, Kitti Tamási, László Grama, Edit Varga, Katalin Sipos
Hepcidin, the key hormone of iron homeostasis is responsible for lowering the serum iron level through its interaction with iron exporter ferroportin. Thus, hepcidin agonists provide a promising opportunity in the treatment of iron disorders caused by lacking or decreased hepcidin expression. We investigated the importance of each of the eight highly conserved cysteines for the biological activity of hepcidin. Eight cysteine mutants were created with site directed mutagenesis. The binding ability of these hepcidin mutants to the hepcidin receptor ferroportin was determined using bacterial two-hybrid system and WRL68 human hepatic cells...
February 12, 2018: Protein Journal
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