To establish the time-sequence relationship between ferritin accumulation and uroporphyrin crystal formation in livers of C57BL/10 mice, a biochemical, morphological and morphometrical study was performed. Uroporphyria was induced by the intraperitoneal administration of hexachlorobenzene plus iron dextran and of iron dextran alone. Uroporphyrin crystal formation started in hepatocytes of mice treated with hexachlorobenzene plus iron dextran at 2 weeks and in mice treated with iron dextran alone at 9 weeks. In the course of time, uroporphyrin crystals gradually increased in size. Uroporphyrin crystals were initially formed in hepatocytes in the periportal areas of the liver, in which also ferric iron staining was first detected. The amount and the distribution of the main storage form of iron in hepatocytes, ferritin, did not differ between the two treatment groups. Ferritin accumulation preceded the formation of uroporphyrin crystals in hepatocytes in both treatment groups. Moreover, uroporphyrin crystals were nearly always found close to ferritin iron. We conclude that uroporphyrin crystals are only formed in hepatocytes in which also iron (ferritin) accumulates. Hexachlorobenzene accelerates the effects of iron in porphyrin metabolism, but does not influence the accumulation of iron into the liver.

Ferritin, Hepatocytes, Hexachlorobenzene, Iron, Liver, Mouse, Uroporphyria, Uroporphyrin,
Cell and Tissue Research
Department of Pathology

Siersema, P.D, Cleton-Soeteman, M.I, de Bruijn, W.C, ten Kate, F.J.W, van Eijk, H.G, & Wilson, J.H.P. (1993). Ferritin accumulation and uroporphyrin crystal formation in hepatocytes of C57BL/10 mice: A time-course study. Cell and Tissue Research, 274(2), 405–412. doi:10.1007/BF00318759