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Cited by 118

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

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

Kato, J, Kobune, M, Kohgo, Y, Sugawara, N, Hisai, H, Nakamura, T, Sakamaki, S, Sawada, N, Niitsu, Y·1996·Journal of Clinical Investigation
DOI 10.1172/jci118875
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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.

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Metadata

Authors
Kato, J., Kobune, M., Kohgo, Y., Sugawara, N., Hisai, H., Nakamura, T., Sakamaki, S., Sawada, N., & Niitsu, Y.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1996-08-15
Volume
98
Issue
4
Pages
923-929
ISSN
0021-9738
DOI
10.1172/jci118875
Cited by
118
References
39
Language
en

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