Iron and uroporphyrin in hepatocytes of inbred mice in experimental porphyria: A biochemical and morphological study

Siersema, Peter D.; Helvoirt, R. P. van; Ketelaars, Diane A. M.; Cleton, Maud I.; Bruijn, W. C. de; Wilson, J. H. P.; Eijk, H.G. Van

doi:10.1002/hep.1840140637

Cited by 14 publications

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“…[30][31][32] In contrast, in Fe dextran-treated wild-type mice, Fe is found in both parenchymal and Kupffer cells, with massive loading in Kupffer cells. 23,41 Previously, it was shown that in ALAtreated SWR mice, large doses of Fe dextran (500 mg Fe/kg) are required to maximize URO accumulation. 24 Perhaps these high doses were needed to produce sufficient Fe accumulation in the parenchymal cells to induce uroporphyria in this mouse strain.…”

Section: Discussionmentioning

confidence: 99%

“…20,43 In addition, no ALA treatment is necessary to cause development of uroporphyria in some mouse strains given Fe dextran alone. 24,41 However, Bechara et al have postulated that metals catalyze the formation of an ALA radical 44 that can release Fe from ferritin in vitro. 45 This group also reported some increases in hepatic non-heme Fe in rats acutely treated with parenteral ALA, 45 or with an inhibitor of ALA dehydrase.…”

Section: Discussionmentioning

confidence: 99%

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Uroporphyria in Hfe mutant mice given 5-aminolevulinate: A new model of Fe-mediated porphyria cutanea tarda

et al. 2001

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Porphyria cutanea tarda (PCT), a liver disease with skin lesions caused by excess liver production of uroporphyrin (URO), is associated with consumption of alcoholic beverages or estrogens, and moderate iron overload. Recently, it has been shown that many PCT patients carry mutations in the HFE gene, which is responsible for hereditary hemochromatosis. Mice homozygous for either the null mutation in the Hfe gene or the C282Y missense mutation rapidly accumulate hepatic parenchymal iron similar to patients with hemochromatosis. Here we investigated whether disruption of the murine Hfe gene would result in hepatic uroporphyria. Mice homozygous for the Hfe-null mutation accumulated high levels of hepatic URO when fed 5-aminolevulinate (ALA). Hfe (؉/؊) mice also accumulated hepatic URO when fed ALA, but at a much slower rate. The amount of accumulated URO in the null mutant mice was similar to that in wild-type mice treated with iron carbonyl in the diet, or injected with iron dextran. Iron in both wildtype and Hfe (؉/؊) mice was mostly in Kupffer cells. In contrast, Hfe (؊/؊) mice had considerable parenchymal iron deposition as well, in a pattern similar to that observed in wild-type mice treated with iron carbonyl. URO accumulation was accompanied by 84% and 33% decreases in hepatic uroporphyrinogen decarboxylase activities in Hfe (؊/؊) and Hfe (؉/؊) mice, respectively. No increases in CYP1A2 or other cytochrome P450s were detected in the Hfe-null mutant mice. We conclude that this experimental model of uroporphyria is a valid model for further investigations into the mechanism of PCT. (HEPATOLOGY 2001;33: 406-412.)

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