title: Iron overload enhances the development of experimental liver cirrhosis in mice.
abstract: The role of iron in initiating liver fibrosis in iron overload diseases is not clearly established. Partly, this is due to the lack of suitable animal models that can produce the full liver pathology seen in genetic hemochromatosis. Recent advances in this field have demonstrated that iron may be interacting with other potential liver-damaging agents. The aim of this study was to investigate if feeding with carbonyl iron (CI) facilitates the development of carbon tetrachloride (CCl4)-induced liver fibrosis in the mouse. Mice were given a diet containing 3% CI and treated with CCl4 intraperitoneally twice weekly and 5% alcohol added to the drinking water for 12 weeks. Hepatic iron content increased 15- and 22-fold in animals receiving CI and CI + CCl4. At histological examination, iron-laden hepatocytes were found in CI treated animals, whereas these were absent in animals not exposed to CI. Mice receiving iron-enriched diet alone showed a mild fibrosis. Conversely, a marked collagen deposition was observed in CCl4 and CI + CCl4 groups. In particular, in this latter group, there was evidence of liver cirrhosis. Biochemical evaluation of collagen content substantiated histologic analysis. These results demonstrate that the addition of iron facilitates the development of cirrhosis in animals exposed to subtoxic doses of CCl4. This model may be useful in exploring the pathogenesis of liver cirrhosis. Moreover, its use in genetically altered mouse strains might provide new insight on the role of iron in fibrosis.
authors.affiliation: Department of Pathophysiology and Experimental Medicine, University of Siena, via A. Moro, I-53100, Siena, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arezzini
authors.forename: Benedetta
authors.initials: B
authors.lastname: Lunghi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lungarella
authors.forename: Concetta
authors.initials: C
authors.lastname: Gardi
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D054354:Iron Carbonyl Compounds; D019190:Iron Overload / Q000150:complications* / Q000378:metabolism; D019266:Iron, Dietary / Q000633:toxicity; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism*; D051379:Mice; D009942:Organometallic Compounds / Q000633:toxicity
chemical_list: D019266:Iron, Dietary; D009942:Organometallic Compounds; D054354:Iron Carbonyl Compounds; D003094:Collagen; D002251:Carbon Tetrachloride