Hepatotoxicity of iron overload: Mechanisms of iron-induced hepatic fibrogenesis

Ramm, Grant A. and Ruddell, Richard G. (2005) Hepatotoxicity of iron overload: Mechanisms of iron-induced hepatic fibrogenesis. Seminars in Liver Disease, 25 4: 433-449. doi:10.1055/s-2005-923315

Author Ramm, Grant A.
Ruddell, Richard G.
Title Hepatotoxicity of iron overload: Mechanisms of iron-induced hepatic fibrogenesis
Journal name Seminars in Liver Disease   Check publisher's open access policy
ISSN 0272-8087
Publication date 2005-11-01
Sub-type Article (original research)
DOI 10.1055/s-2005-923315
Open Access Status DOI
Volume 25
Issue 4
Start page 433
End page 449
Total pages 14
Editor Bruce R. Bacon
Language eng
Abstract While iron is a vital requirement for normal cellular physiology, excessive intestinal absorption of iron as seen in hemochromatosis leads to its deposition in parenchymal cells of various organs such as the liver, heart, and pancreas, resulting in cellular toxicity, tissue injury, and organ fibrosis. Cellular injury is induced by iron-generated oxyradicals and peroxidation of lipid membranes. In the liver, lipid peroxidation results in damage to hepatocellular organelles, such as mitochondria and lysosomes, which is thought to contribute to hepatocyte necrosis and apoptosis, and ultimately lead to the development of hepatic fibrogenesis. Hepatic stellate cells are central to the development of hepatic fibrosis, as they can be activated into collagen-producing myofibroblasts. Numerous potential stimuli associated with hepatic iron overload and iron-induced hepatocellular injury have been assessed in an attempt to explain stellate cell transformation in hemochromatosis. Stellate cell activation and fibrosis appear to be regulated by a series of events involving cellular interaction between resident and nonresident cells of the liver, the sequestration of free iron versus the transport and storage of mobilizable iron, and extracellular matrix remodeling as well as intracellular signaling events associated with inflammatory and fibrogenic cytokines.
Keyword Iron
Hepatic fibrosis
Hepatic stellate cell
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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