Semin Liver Dis 2005; 25(4): 433-449
DOI: 10.1055/s-2005-923315
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Hepatotoxicity of Iron Overload: Mechanisms of Iron-Induced Hepatic Fibrogenesis

Grant A. Ramm1 , 2 , Richard G. Ruddell2
  • 1Associate Professor and Head, The Queensland Institute of Medical Research, Brisbane, Australia
  • 2The Hepatic Fibrosis Group, The Queensland Institute of Medical Research, Brisbane, Australia
Further Information

Publication History

Publication Date:
29 November 2005 (online)

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.

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Grant A RammPh.D. 

Head, Hepatic Fibrosis Group, The Queensland Institute of Medical Research, PO Box Royal Brisbane and Women's Hospital

Herston, Brisbane, QLD., 4029, Australia

Email: Grant.Ramm@qimr.edu.au

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