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Results for “Iron Overload”

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At least 973 records · Page 54Linked to original sources
PubMed2000

Quantitative mapping of transverse relaxivity (1/T(2)) in hepatic iron overload: a single spin-echo imaging methodology.

Recent research into the non-invasive assessment of hepatic iron concentrations using magnetic resonance imaging has shown that the proton transverse relaxivity (1/T(2)) varies linearly with liver iron concentration. However, the development of an image-based system for the assessment of hepatic iron distribution has been confounded by the presence of motion induced artifacts in the T(2)-weighted images. We report on the development of a single spin-echo imaging methodology that enables the generation of transverse relaxivity maps over the liver. A simple smoothing technique is used to accommodate the image intensity perturbations caused by abdominal motion. The relaxivity maps are consistent with the variation of iron concentration throughout the liver. A Parzen density estimate and histogram of the relaxivity distribution are generated to assist in the visual assessment of the degree and variability of T(2) shortening with liver iron loading. It was found that one or two Gaussian functions could be used to characterize the relaxivity distributions with a small number of parameters. We propose that this methodology may be used in the clinical setting to monitor hepatic iron concentrations in the advent of an accurate transverse relaxivity calibration curve.

Adolescent↗
PubMed1978

Formation of asbestos bodies under the influence of parenteral iron overload.

The effect of parenteral administration of iron (dextran) on the number of asbestos fibers in the lungs, formation of asbestos bodies and the development of interstitial fibrosis was studied in guinea pigs exposed intratracheally to anthophyllite dust. The treatment did not accelerate, either qualitatively or quantitatively, the formation of asbestos bodies or retard the development of interstitial fibrosis. The number of naked asbestos fibers was also similar in anthophyllite-inoculated animals to those similarly inoculated, but having had, additionally, a previous saturation with iron.

Animals↗
PubMed1965

IRON OVERLOAD.

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Humans↗
PubMed2002

Iron overload decreases the protective effect of tumour necrosis factor-alpha on rat hepatocytes exposed to oxidative stress.

BACKGROUND: Intracellular iron can participate in the formation of free radicals, leading to liver cell damage. This may be prevented by the ability of ferritin to oxidize and store iron. Tumour necrosis factor alpha (TNF-alpha) has been shown to increase the ferritin synthesis. In the liver, cytokines are secreted by activated Kupffer cells and T-lymphocytes. The aim of this study was to investigate the effects of TNF-alpha on normal and iron-loaded rat hepatocytes exposed to oxidative stress. METHODS: Primary cultures of hepatocytes from rats fed a normal rat chow or a carbonyl iron-enriched diet were incubated with TNF-alpha before incubation with tert-butyl hydroperoxide. Malondialdehyde concentrations, activities of lactate dehydrogenase, ferritin H and manganese superoxide dismutase mRNA and ferritin H protein were analysed. The total amounts of glutathione and chelatable iron were measured. RESULTS: TNF-alpha diminished the concentrations of malondialdehyde and activities of lactate dehydrogenase in hepatocytes exposed to tert-butyl hydroperoxide. This was seen in hepatocytes from normal but not iron-loaded animals. The transcription of manganese-superoxide dismutase mRNA was increased in both cell types, whereas total glutathione contents of cells were unaffected. The transcription and translation of ferritin H was induced in cells from normal but not from iron-loaded animals. The amount of chelatable iron was significantly lowered only in hepatocytes from normal rats. CONCLUSIONS: TNF-alpha protects rat hepatocytes from normal but not iron-loaded rats from oxidative stress. The protection may be due to an induction of the ferritin synthesis.

Animals↗
PubMed1997

The effect of iron overload in the hearts of patients with beta-thalassemia.

BACKGROUND AND HYPOTHESIS: An important complication of beta-thalassemia is iron deposition in cardiac tissues resulting in fibrosis and dysfunction. Our aim was the investigation of the possible clinical effect of iron loading in the heart of patients with beta-thalassemia prior to the appearance of symptoms of depressed systolic function. METHODS: Thirty-five patients with beta-thalassemia, of whom 24 had the major type (Group 1) and 11 had the intermedia type (Group 2) were studied. Eleven age- and gender-matched controls were also studied (Group 3). All patients were evaluated echocardiographically and were shown to have normal left ventricular systolic function and dimensions. Serum ferritin, atrial natriuretic peptide (ANP), left atrial diameter (LAD), peak early mitral inflow velocity (E), peak late mitral inflow velocity (A), E/A ratio, deceleration time of the mitral inflow E wave (DT), and isovolumic relaxation time (IVRT) were measured. RESULTS: Univariate analysis showed that both groups of patients had similarly increased LAD and ANP plasma levels. Group 1 had a higher E/A ratio (2.27 +/- 0.88) SS than Group 2 (1.69 +/- 0.47, p = 0.05) and Group 3 (1.50 +/- 0.38, p = 0.01). Serum ferritin was significantly higher in Group 1 (3.526 +/- 0.352) than in Group 2 (2.808 +/- 0.288, p < 10(-5) and Group 3 (2.139 +/- 0.124, p < 10(-5). Multivariate analysis showed that ANP is a factor that is affected by the LAD and E/A ratio and that serum ferritin levels affect the LAD and E/A ratio. CONCLUSIONS: Although LAD and ANP levels are increased in patients with beta-thalassemia, the increased serum ferritin levels of patients seem to affect left atrial size and E/A ratio. ANP secretion is consecutively affected by these factors.

Adult↗
PubMed2005

Primary iron overload with inappropriate hepcidin expression in V162del ferroportin disease.

Ferroportin disease (hemochromatosis type 4) is a recently recognized disorder of human iron metabolism, characterized by iron deposition in macrophages, including Kupffer cells. Mutations in the gene encoding ferroportin 1, a cellular iron exporter, are responsible for this iron storage disease, inherited as an autosomal dominant trait. We present clinical, histopathological, and radiological findings in a family with the most common ferroportin mutation, V162del. In the index case, the disorder is characterized by abundant deposition of hemosiderin in all tissues investigated (mesenteric lymph node, liver, gastric and duodenal mucosa, and also in squamous cell carcinoma of the lung). The radiological findings indicated the presence of excess iron in bone marrow and spleen. Despite a significant burden of iron, no features of chronic liver disease were found in affected members of the family, including individuals aged up to 80 years. Hyperferritinemia greater than 1,000 microg/L was a penetrant biochemical finding before the second decade in life and was associated with significantly increased serum concentrations of pro-hepcidin that correlated positively with urinary hepcidin concentrations. In conclusion, the systemic iron burden in ferroportin disease is not a sufficient cause for chronic liver disease. In patients with most, but not all, ferroportin mutations, retention of iron in macrophages of the liver and other organs may protect against damage to parenchymal cells. Finally, macrophage iron storage in ferroportin disease is associated with elevated serum pro-hepcidin levels.

Adolescent↗
PubMed1999

The effects of dietary iron overload on fumonisin B1-induced cancer promotion in the rat liver.

The present study was performed to determine whether excess hepatic iron modulates the cancer-initiating and promoting properties of FB1. Thirty-eight male F344 rats were divided into four dietary treatment groups: (i) control diet (AIN, n = 8); (ii) FB1 250 mg/kg diet (FB1, n = 10); (iii) 1-2% carbonyl iron (CI, n = 10); or (iv) FB1 plus iron loading (FB1/CI, n = 10) for 5 weeks (2 x 2 factorial design). Hepatic iron concentrations in iron-loaded animals at 5 weeks were 444 +/- 56 (CI) and 479 +/- 80 micromol/g dry weight (FB1/CI) (mean +/- SEM). All the FB1-fed rats, in the presence or absence of CI, developed a toxic hepatitis with a 4-fold rise in serum alanine transaminase (ALT) levels. FB1 appeared to augment iron-induced hepatic lipid peroxidation, as measured by the generation of thiobarbituric acid reacting substances (TBARS) in liver homogenates (P < 0.0001). Morphometric analysis showed that FB1 caused a significantly greater mean +/- SEM number of 'enzyme-altered' foci and nodules per cm2 (5.34 +/- 1.42 vs. 1.50 +/- 0.52, P < 0.05), as well as a greater area (%) of liver occupied by foci and nodules (0.33 +/- 0.12% vs. 0.05 +/- 0.03%, P < 0.001), compared with FB1/CI. The addition of FB1 to dietary iron loading caused a shift in distribution of iron from hepatocytes to Kupffer cells, probably due to phagocytosis of necrotic iron-loaded hepatocytes. In conclusion, (i) FB1 appears to cause toxicity in the liver independently from effects on lipid peroxidation; (ii) FB1 has a potentiating effect on iron-induced lipid peroxidation; and (iii) dietary iron loading appears to protect against the cancer promoting properties of FB1, possibly due to a stimulatory effect of iron on hepatocyte regeneration.

Animals↗
PubMed2006

RNA silencing of the mitochondrial ABCB7 transporter in HeLa cells causes an iron-deficient phenotype with mitochondrial iron overload.

X-linked sideroblastic anemia with ataxia (XLSA/A) is caused by defects of the transporter ABCB7 and is characterized by mitochondrial iron deposition and excess of protoporphyrin in erythroid cells. We describe ABCB7 silencing in HeLa cells by performing sequential transfections with siRNAs. The phenotype of the ABCB7-deficient cells was characterized by a strong reduction in proliferation rate that was not rescued by iron supplementation, by evident signs of iron deficiency, and by a large approximately 6-fold increase of iron accumulation in the mitochondria that was poorly available to mitochondrial ferritin. The cells showed an increase of protoporphyrin IX, a higher sensitivity to H(2)O(2) toxicity, and a reduced activity of mitochondrial superoxide dismutase 2 (SOD2), while the activity of mitochondrial enzymes, such as citrate synthase or succinate dehydrogenase, and ATP content were not decreased. In contrast, aconitase activity, particularly that of the cytosolic, IRP1 form, was reduced. The results support the hypothesis that ABCB7 is involved in the transfer of iron from mitochondria to cytosol, and in the maturation of cytosolic Fe/S enzymes. In addition, the results indicate that anemia in XLSA/A is caused by the accumulation of iron in a form that is not readily usable for heme synthesis.

ATP-Binding Cassette Transporters↗
PubMed2000

[Premalignant lesions and hepatocellular carcinoma on non cirrhotic liver overloaded with iron].

A 68-year old mildly obese Caucasian man underwent hepatic resection for multinodular hepatocellular carcinoma which had developed in the left lobe of a non-cirrhotic liver. The only risk factors found were heavy drinking, smoking, and serum markers of hepatitis B virus without virus genome in hepatocytes. The non tumoral liver was mildly fibrotic and iron overloaded (hepatic iron index: 1.6) with three types of iron-free lesions: (i) periportal clear hepatocyte foci, (ii) hyperplastic nodules and (iii) dysplastic or neoplastic nodules with well to moderately-differentiated hepatocellular carcinoma. The genetic investigation was negative for the C282Y and the H63D mutations of the HFE gene. This observation illustrates the multistep process of carcinogenesis in the non-cirrhotic liver and raises the question of i) the origin of this iron overload possibly linked to insulin resistance syndrome and ii) the role of iron as a co-carcinogen.

Aged↗