Carbonyl-iron supplementation induces hepatocyte nuclear changes in BALB/CJ male mice

Background/Aims: In humans, chronic iron excess may induce hepatic fibrosis and/or hepatocellular carcinoma. This work was undertaken to investigate h epatic iron overload outcome in iron-overloaded mice. Methods: BALB/cJ male mice received supplements of 0, 0.5, 1.5 and 3% carbo nyl-iron for 2, 4, 8 and 12 months. Histological staining, immunohistochemi stry using ferritin antibodies and electron microscopic studies were perfor med on liver. Liver iron concentration was measured biochemically, Mitotic index and hepatocyte nuclear size were evaluated on Feulgen-stained slides. Results: Liver iron concentration was increased, reaching 13 times control value after 12 months in 3% iron-overloaded mice, and iron was found predom inantly in hepatocytes, with a porto-centrolobular decreasing gradient. Nei ther hepatic fibrosis nor hepatocellular carcinoma was found. Perls' stain positive inclusions containing ferritin were found within hepatocyte nuclei in 3%-overloaded mice, Electron microscopy disclosed that inclusions consi sted of ferritin particle aggregates without a limiting membrane. Mice over loaded with 3% iron for 12 months showed larger hepatocyte nuclei than cont rol mice and a mitotic index increase with presence of abnormal tripolar mi totic figures. In addition, some iron-free hepatocytes were observed. Conclusions: Carbonyl-iron supplementation produces significant iron overlo ad in mice but does not result in liver fibrosis or hepatocellular carcinom a after 12 months. However, nuclear changes were produced in hepatocytes, a nd occasional iron-free hepatocytes were observed: these may represent pren eoplastic changes caused by iron overload.