Iron and uroporphyrin in hepatocytes of inbred mice in experimental porphyria: a biochemical and morphological study.
Hexachlorobenzene-induced porphyria is iron dependent and characterized by the decreased activity of uroporphyrinogen decarboxylase and the accumulation of porphyrins in the liver. To examine the relationship between iron and porphyrins in liver tissue, we performed a biochemical and morphological (histological, ultrastructural and morphometrical) study in the livers of C57BL/10 mice. Mice were treated with hexachlorobenzene, iron dextran or the combination of hexachlorobenzene and iron dextran. An accumulation of porphyrins and an increased total iron content were found not only in the livers of mice treated with hexachlorobenzene and iron dextran but also in mice treated with iron dextran alone. In contrast, the amount of porphyrins was only slightly increased in the livers of mice treated with hexachlorobenzene alone. Needle-like structures, representing uroporphyrin crystals, were observed, histologically and ultrastructurally, in hepatocytes of mice treated with hexachlorobenzene and iron dextran and with iron dextran alone. Uroporphyrin crystals and ferritin iron were found in the same hepatocyte. A single uroporphyrin crystal, surrounded by ferritin iron, was observed in a hepatocyte of a mouse treated with hexachlorobenzene alone. Both in the livers of mice treated with hexachlorobenzene and iron dextran and in the livers of mice treated with iron dextran alone, morphometrical analysis showed that an increased area fraction of uroporphyrin crystals was associated with an increased area fraction of ferritin iron in hepatocytes.


CONCLUSIONS
In C57BL/10 mice, experimental porphyria can be induced by iron overload alone; uroporphyrin crystals and ferritin iron are located in the same hepatocyte; and the morphological co-occurrence of uroporphyrin crystals and ferritin iron in hepatocytes suggests a role for iron (as ferritin) in the pathogenesis of porphyria.
Siersema
P D
PD
Department of Internal Medicine, University Hospital Rotterdam-Dijkzigt, The Netherlands.
van Helvoirt
R P
RP
Ketelaars
D A
DA
Cleton
M I
MI
de Bruijn
W C
WC
Wilson
J H
JH
van Eijk
H G
HG
D000818:Animals; D004338:Drug Combinations; D006581:Hexachlorobenzene; D007501:Iron / Q000378:metabolism*; D007505:Iron-Dextran Complex; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D011164:Porphyrias / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014578:Uroporphyrins / Q000378:metabolism*
D004338:Drug Combinations; D014578:Uroporphyrins; D006581:Hexachlorobenzene; D007505:Iron-Dextran Complex; D007501:Iron