Iron in liver

It has been proposed that a low molecular weight phosphoprotein of phosvitin nature (47) which binds iron with high affinity may be involved in the cytosolic transport of iron in liver cells (48, 49), but no energized uptake of iron has been demonstrated such as in isolated rat liver mitochondria using a Fe(III)-phosvitin from avian egg yolk (mol wt 40,000) as the substrate (50). The biochemical significance of the cytosolic iron binding phosphoprotein is therefore still uncertain. 

Olynyk, J., Hall, R, Sallie, R., Reed, W Shilkin, K., Mackinnon, M. Computerized measurement of iron in liver biopsies a comparison with biochemical iron measurement. Hepatology 1990 12 26-30... 

Bonkovsky HL, Banner BE, Lambrecht RW, Rubin RB. Iron in liver diseases other than chemo chromatosis. Semin Liver Dis 1996 16(l) 65-82. 

The recognition of metals as integral parts of enzyme systems has led to investigations aimed at elucidating their functional role in the catalytic process. Of the transition metals, iron has been best studied in this regard. This stems from several circumstances first, the characteristic color of the heme pigments early called attention to this element second, the concentration of iron in liver, muscle, and red cells is high, relative to the other transition elements third, the functional heme unit can be isolated with... 

Treatment of hereditary hemochromatosis is therapeutic phlebotomy (discussed earlier). This method is safe, effective, and life saving, and ideally should begin before symptoms develop. Serum ferritin levels are used as a surrogate marker for estimating total-body iron stores. Morphologic studies and quantitative determination of iron in liver tissue obtained by biopsy have been used in the assessment of early hereditary hemochromatosis and the degree of liver injury. 

Reference and Pathological Values for Copper in Liver, Duodenum and Fibroblasts, and for Iron in Liver ... 

D. E. Nixon, J. Butz, S. J. Ekdahl, M. F. Burritt, K. R. Neubauer, and R. E. Wolf, Determination of Copper and Iron in Liver Tissue Using DRC ICP-MS, PerkinElmer LAS Application Note, 2004, http //las.perkinehner.com/content/applicationnotes/ app elandrccopperironinliver.pdf. 

Determination of Copper and Iron in Liver Tissue Using DRC ICP-MS, PerkinElmer LAS Application Note, 2004, http //las.perkinelmer.com/content/apphcationnotes/app elandrccopperironinliver.pdf. 

Poli, G., Dianzani, M.U., Cheeseman, K.H., Slater, T.F., Lang, J. and Esterbauer, H. (1985). Separation and characterization of the aldehydic products of lipid peroxidation stimulated by carbon tetrachloride or ADP-iron in isolated rat hepatocytes and rat liver microsomal suspensions. Biochem. J. 227, 629-638,... 

There is very little data on ROM production in haemochromatosis in humans. Increases in thiobarbituric acid reactants in plasma were associated with increases in non-transferrin-bound free iron. However, other indices of lipid peroxidation were no different from controls (Peters eta/., 1985). There are no studies of in vivo lipid peroxidation in humans. It is also of interest that levels of antioxidant defences in liver biopsies from patients with haemochromatosis are normal (Selden et /., 1980). 

Poli, G., Albano, E., Biasi, F., Cecchini, G., Carini, R-, Bel-lomo, G. and Dianzani, M.U. (1985). Lipid peroxidation stimulated by carbon tetrachlorde or iron and hepatocyte death protective effect of vitamin E. In Free Radicals in Liver Injury (eds. G. Poli, K.H. Cheeseman, M.U. Dinzani and T.F. Slater) pp. 127-134. Oxford, IRL Press. 

Shaw, D.S. and Jayatilleke, E. (1992). The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury. Life Sci. 50, 2045-2052. 

Adachi, S., Takemoto, K., Hirosuc, T. and Hosogai, Y. (1993). Spontaneous and 2-nitropropane induced levels of 8-hydroxy-2 -deoxyguanosine in liver DNA of rats fed iron-deficient or manganese- and copper-deficient diets. Carcinogenesis 14, 265-268. 

Iron appeared to reduce the effects of orally or subcutaneously administered lead on blood enzyme and liver catalase activity (Bota et al. 1982). Treatment of pregnant hamsters with iron- or calcium-deficient diets in conjunction with orally administered lead resulted in embryonic or fetal mortality and abnormalities (ranting, edema) in the litters, while treatment with complete diets and lead did not (Carpenter 1982). Inadequate levels of iron in association with increased body burdens of lead enhanced biochemical changes associated with lead intoxication (Waxman and Rabinowitz 1966). Ferrous iron was reported to protect against the inhibition of hemoglobin synthesis and cell metabolism by lead it has been speculated that iron competes with lead uptake by the cell (Waxman and Rabinowitz 1966). In... 

IX is accompanied by its transport back into the mitochondria whence it came, to undergo oxidation of its methylene groups to protoporphyrin IX and insertion of iron to yield the end product, haem. The two major sites of haem biosynthesis are erythroid cells, which synthesize around 85 % of the body s haem groups, and the liver, which synthesizes most of the remainder. A major function of haem in liver is as the prosthetic group of cytochrome P450, the importance of which in detoxification has been discussed in Chapter 2. The liver cell must synthesize cytochrome P450 throughout its lifetime in quantities that vary with conditions. In contrast, the... 

Figure 8.1 Body iron stores and daily iron exchange. The figure shows a schematic representation of the routes of iron movement in normal adult male subjects. The plasma iron pool is about 4 mg (transferrin-bound iron and non-transferrin-bound iron), although the daily turnover is over 30 mg. The iron in parenchymal tissues is largely haem (in muscle) and ferritin/haemosiderin (in hepatic parenchymal cells). Dotted arrows represent iron loss through loss of epithelial cells in the gut or through blood loss. Numbers are in mg/day. Transferrin-Tf haemosiderin - hs MPS - mononuclear phagocytic system, including macrophages in spleen and Kupffer cells in liver.

Although many animal models for iron overload exist, some mimicking certain aspects of HH, the 32-microglobulin knockout mouse is of special interest as it revealed for the first time crucial aspects of the pathogenesis of human HH in an animal model, and also because it underlines the important links between iron metabolism and the immune system. Hepatic iron overload in 32-microglobulin ( 32m)-deficient mice appeared to be similar to that found in HH, with pathological iron depositions occurring predominantly in liver parenchymal cells (de Sousa et ah,... 

One of the most notable features of this inherited defect of iron homeostasis (Chapter 9) is the ability of individuals to accumulate large amounts of iron over many years and yet show no apparent adverse effects. This may in part be due to the ability of tissues, notably the liver, to increase their iron stores gradually over a long period of time, successfully sequestrating excess iron into ferritin and, predominantly, haemosiderin. However with time the excessive deposition of iron will cause a variety of toxic effects including diabetes and arthritis which are caused by deposition of iron in these tissues. Removal of this iron by venesection can often reduce these iron-induced symptoms. 

DNA damage by iron chelators has been shown by Cragg et al. [84]. These authors showed that various iron chelators affected the hydrogen peroxide-mediated DNA damage in iron-loaded liver cells in different ways. Thus, desferrithiocin was protective and desferri-oxamine had no effect, while l,2-dimethyl-3-hydroxypyrid-4-one (LI) enhanced oxidative DNA damage. It has been suggested that the oxidative effect of LI depended on stoichiometry of Fe—LI complexes. 

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