title: The role of iron in experimental porphyria and porphyria cutanea tarda.
abstract: Porphyria cutanea tarda (PCT) and experimental porphyria are characterized by a decreased activity of the enzyme uroporphyrinogen decarboxylase, and accumulation of uroporphyrins and heptacarboxylporphyrins in the liver. Iron (Fe) plays an important role in PCT and experimental porphyria. Biochemically and electron microscopically, we examined the relationship between Fe and porphyrins in liver tissue of C57BL/10 mice made porphyric by administration of iron dextran as Imferon (IMF), and in liver biopsies of patients with symptomatic PCT. Accumulation of uroporphyrins and heptacarboxylporphyrins, and an increased amount of Fe were observed in livers of mice treated with IMF and in liver biopsies of patients with PCT. In mice treated with IMF, the activity of uroporphyrinogen decarboxylase was decreased. Both in livers of mice treated with IMF and in livers of patients with PCT, needle-like structures, representing uroporphyrin crystals, were observed by electron microscopy. Uroporphyrin crystals and Fe (as ferritin) were observed in the same hepatocyte. Moreover, there was a striking morphological correlation between uroporphyrin crystals and ferritin-Fe, suggesting a role for (ferritin-)Fe in the pathogenesis of porphyria.
authors.affiliation: Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
authors.forename: P D
authors.initials: PD
authors.lastname: Siersema
authors.forename: R P
authors.initials: RP
authors.lastname: van Helvoirt
authors.forename: M I
authors.initials: MI
authors.lastname: Cleton-Soeteman
authors.forename: W C
authors.initials: WC
authors.lastname: de Bruijn
authors.forename: J H
authors.initials: JH
authors.lastname: Wilson
authors.forename: H G
authors.initials: HG
authors.lastname: van Eijk
mesh_terms: D000818:Animals; D005293:Ferritins / Q000032:analysis; D006485:Hemosiderin / Q000032:analysis; D006801:Humans; D007501:Iron / Q000032:analysis*; D007505:Iron-Dextran Complex / Q000008:administration & dosage; D008099:Liver / Q000737:chemistry* / Q000648:ultrastructure; D008247:Lysosomes / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D017119:Porphyria Cutanea Tarda / Q000378:metabolism*; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism*; D014578:Uroporphyrins / Q000032:analysis
chemical_list: D014578:Uroporphyrins; D007505:Iron-Dextran Complex; D005293:Ferritins; D006485:Hemosiderin; D007501:Iron