Advertisement

Research Article Free access | 10.1172/JCI118875

Hepatic iron deprivation prevents spontaneous development of fulminant hepatitis and liver cancer in Long-Evans Cinnamon rats.

J Kato, M Kobune, Y Kohgo, N Sugawara, H Hisai, T Nakamura, S Sakamaki, N Sawada, and Y Niitsu

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Kato, J. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Kobune, M. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Kohgo, Y. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Sugawara, N. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Hisai, H. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Nakamura, T. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Sakamaki, S. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Sawada, N. in: PubMed | Google Scholar

Fourth Department of Internal Medicine, Department of Public Health, Sapporo Medical University School of Medicine, Japan.

Find articles by Niitsu, Y. in: PubMed | Google Scholar

Published August 15, 1996 - More info

Published in Volume 98, Issue 4 on August 15, 1996
J Clin Invest. 1996;98(4):923–929. https://doi.org/10.1172/JCI118875.
© 1996 The American Society for Clinical Investigation
Published August 15, 1996 - Version history
View PDF
Abstract

Several clinical studies have suggested that excess hepatic iron accumulation is a progressive factor in some liver diseases including chronic viral hepatitis and hemochromatosis. However, it is not known whether iron-induced hepatotoxicity may be directly involved in hepatitis, cirrhosis, and liver cancer. The Long-Evans Cinnamon (LEC) rat, which accumulates excess copper in the liver as in patients with Wilson's disease, is of a mutant strain displaying spontaneous hemolysis, hepatitis, and liver cancer. We found previously that LEC rats harbored an additional abnormality: accumulation of as much iron as copper in the liver. In the present study, we compared the occurrence of hepatitis and liver cancer in LEC rats fed an iron-deficient diet (ID) with those in rats fed a regular diet (RD). The RD group showed rapid increments of hepatic iron concentrations as the result of hemolysis, characteristics of fulminant hepatitis showing apoptosis, and a 53% mortality rate. However, no rats in the ID group died of fulminant hepatitis. Hepatic iron, especially "free" iron concentration and the extent of hepatic fibrosis in the ID group were far less than those of the RD group. At week 65, all rats in the RD group developed liver cancer, whereas none did in the ID group. These results suggest that the accumulation of iron, possibly by virtue of synergistic radical formation with copper, plays an essential role in the development of fulminant hepatitis, hepatic fibrosis, and subsequent hepatocarcinogenesis in LEC rats.

Version history
  • Version 1 (August 15, 1996): No description
Advertisement
Advertisement