Regional distribution of copper, zinc and iron in the brain in Long-Evans Cinnamon (LEC) rats with a new mutation causing hereditary hepatitis

Sakata, Naoki; Ikeda, Toshiko; Sugawara, Chieko; Kohgo, Yutaka; Kato, Junji; Takeichi, Noritoshi

doi:10.1016/0006-8993(92)91587-5

Cited by 22 publications

(15 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, an accumulation of label in the hip pocampus and amygdala after chronic admin istration of 65-Zn [24], plus elevated levels of zinc in the hippocampus as detected by other methods [25], supports the general validity of histochemical staining patterns for metals.…”

Section: Relationship Of Glial Mt To Cns Metalsmentioning

confidence: 82%

Glial Metallothionein

Young¹

1994

Biological Signals

View full text Add to dashboard Cite

The metal-binding protein, metallothionein (MT) has been found to be primarily produced by astrocytes in the rat and human brain. This review discusses the relationship of glial MT to the distribution of metals in the brain, possible roles of MT in the regulation of glial enzymes and other glial proteins, and the possible role of a subset of MT-immunoreactive glia, the Gomori-positive astrocytes, in defending against toxic metals that enter the brain via circumventricular organs. The possible involvement of MT-containing astrocytes in degenerative brain disorders in also briefly discussed.

show abstract

Section: Relationship Of Glial Mt To Cns Metalsmentioning

confidence: 82%

Glial Metallothionein

Young¹

1994

Biological Signals

View full text Add to dashboard Cite

show abstract

“…On the other hand, we demonstrated previously that LEC rats accumulated as much iron as copper in the liver and brain (14,15) and had elevated serum transferrin levels, an abnormality in iron metabolism. Therefore, we have postulated that excess hepatic iron accumulation, in addition to copper accumulation, contributes to the development of the liver injury in LEC rats.…”

Section: Introductionmentioning

confidence: 77%

“…To determine serial changes of hepatic copper and iron levels, 83 rats were fed with RD and 50 rats with ID after week 6 when 5 rats were killed to obtain pretreatment values, and thereafter 5 rats in each group were killed at weeks 7,12,14,15,16,18,20,24,32, and 65. In the RD group, 33 rats died of fulminant hepatitis between weeks 14 and 16, whereas all the rats in the ID group survived the observation period (week 65).…”

Section: Resultsmentioning

confidence: 99%

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

Kato¹,

Kobune²,

Kohgo³

et al. 1996

J. Clin. Invest.

138

View full text Add to dashboard Cite

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.

show abstract

“…However, no significant differences were found between copper contents in the cerebral cortex of LEC and control rats at 20 weeks of age [27]. Sugawara et al [37] reported that the copper contents of the brain regions, including the cerebral cortex of LEC rats were slightly (c.a. 1.2 to 1.5 folds) but significantly higher than those in control rats at 32 weeks of age.…”

Section: Introductionmentioning

confidence: 92%

“…Therefore, LEC rats provide a useful experimental model for Wilson disease [19,31]. The copper contents in the brains of LEC rats have been reported to be significantly lower than those in the brains of control rats at 4 and 7 weeks of age [27,37]. Copper contents in some regions of the brain, such as the cerebellum, in LEC rats were found to be slightly (c.a.…”

Section: Introductionmentioning

confidence: 99%