title: Pathology of dietary carbonyl iron overload in rats.
abstract: Serial light microscopic and ultrastructural studies were performed in rats with experimental iron overload produced by dietary supplementation with carbonyl (elemental) iron over a 12-month period. Hepatic iron increased rapidly to concentrations approximately 40 to 90 times those of control rats by 3 months. Within the liver, iron deposition was initially confined to periportal (zone 1) hepatocytes but subsequently extended to midzonal (zone 2) and centrilobular (zone 3) hepatocytes. Reticuloendothelial cell deposits of iron increased gradually and became prominent after 3 months. At this time, morphologic evidence of hepatocellular injury was mild and subtle with occasional foci of spotty necrosis and ultrastructural subcellular organelle damage. By 8 months, iron deposition was massive. Portal areas were enlarged with collections of iron-loaded macrophages and increased collagenous tissue. This portal fibrous tissue extended between periportal (zone 1) hepatocytes at sites of maximal iron deposition and around iron-loaded Kupffer cells and macrophages. At 12 months, the periportal (zone 1) fibrosis was more pronounced. These serial morphologic studies are the first to demonstrate the production of hepatic fibrosis by chronic dietary iron overload. This experimental model may reproduce important components of the pathophysiologic sequence of chronic liver damage seen in iron overload states in humans.
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Ohio.
authors: C H
authors: CH
authors: Park
authors: B R
authors: BR
authors: Bacon
authors: G M
authors: GM
authors: Brittenham
authors: A S
authors: AS
authors: Tavill
mesh_terms: D000818:Animals; D004032:Diet; D006432:Hemochromatosis / Q000473:pathology; D007501:Iron / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008099:Liver / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
chemical_list: D007501:Iron