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Rapid induction of hepatic fibrosis in the gerbil after the parenteral administration of iron‐dextran complex
Author(s) -
Carthew Philip,
Edwards Richard E.,
Smith Andrew G.,
Dorman Barbara,
Francis Jean E.
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840130322
Subject(s) - gerbil , medicine , fibrosis , dextran , pharmacology , pathology , chemistry , biochemistry , ischemia
The parenteral administration of iron‐dextran complex to gerbils caused hepatic hemosiderosis and fibrosis after 6 wk. Type I and III collagen synthesis in the liver developed from perisinusoidal stellate cells that are often referred to as myofibroblasts. Immunohistologically these cells were shown to have large intracellular deposits of ferritin. The hepatic fibrosis appeared to be associated with aggregates of these cells rather than the aggregates of Kupffer cells, which also occur in hemosiderosis in the liver. No appreciable necrosis of hepatocytes to trigger the fibrotic response was found, so that the fibrosis appeared to be related to the accumulation of ferritin in the perisinusoidal stellate cells. In contrast, rats and mice did not accumulate ferritin in their perisinusoidal cells or develop hepatic fibrosis in response to parenterally administered iron, although they accumulated similar or greater amounts of total iron in their livers. The rapid induction of hepatic fibrosis in gerbils in response to parenterally administered iron will provide a model to investigate the mechanism of induction of collagen deposition in response to iron overload and a means of quickly evaluating therapeutic treatments for iron overload–induced fibrosis in vivo using iron‐chelating drugs. (H EPATOLOGY 1991;13:534–539.)