Abstract
Long-Evans Cinnamon rats are an animal model of Wilson disease with a compound load of copper and iron. However, the mechanisms of the high mortality rate from fulminant hepatitis in the rats remain undetermined. In this study, phlebotomy as an alternative for an iron-deficient diet was investigated to modify hepatitis in the rats. One group of female rats was treated with phlebotomy twice a week, and the other group received blood tests only every 2 weeks. Liver specimens were examined for biochemical non-heme iron and copper, and histochemical trivalent iron. Although all rats examined had icteric hepatitis around the age of 20 weeks, the mortality of fulminant hepatitis was lower in phlebotomized rats than in control rats (1/18 versus 8/20, p<0.05). Phlebotomy not only ameliorated the severity of hepatitis, but also reduced serum malondialdehyde. Non-heme iron in the liver was the greatest in victims of fulminant hepatitis in the control group. There was no difference in the hepatic copper content between the two groups. The prognosis of hepatitis in the rats with Wilson disease was hepatic non-heme iron-dependent, and iron removal by phlebotomy was an effective prophylaxis against fulminant hepatitis.
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