Effects of dietary vitamin E on clinical course and plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities in hereditary hepatitis of LEC rats.
Long-Evans Cinnamon (LEC) rats are autosomal recessive mutants that develop hepatitis and hepatocellular carcinoma. Because copper accumulates in the livers of these rats, and some of their clinical and pathological features are similar to those of patients with Wilson's disease, LEC rats are proposed as an animal model of Wilson's disease. It has been thought that unbound copper generates free radicals, which act as hemolytic and hepatocytotoxic agents. To examine the effects of vitamin E as an antioxidant on hereditary hepatitis in LEC rats, we fed 3-week-old rats for 25 weeks either vitamin E-deficient, control, or vitamin E-supplemented diets which contained < 0.01 mg of total tocopherols, 2 mg of d,l-alpha-tocopheryl acetate (2 I.U.), and 58.5 mg of d,l-alpha-tocopheryl nicotinate (50 I.U.), respectively, per 100 mg of feed. In males, body weight loss was first observed in the vitamin E-deficient group, and mean ages at which jaundice occurred were in the order: deficient younger than control younger than supplemented groups. The ages when plasma glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities began to increase sharply and peaked followed the same order. Thus, it is likely that free radicals are involved in jaundice and hepatitis in LEC male rats, and they are a model for studying the relationship of copper, free radicals, and hepatitis. Conversely, in females, no apparent differences in clinical and biochemical changes were observed among the three groups. Causes for the discrepancy between the sexes remain to be clarified.
Yamazaki
K
K
Laboratory Animal Research Center, Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Ohyama
H
H
Kurata
K
K
Wakabayashi
T
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood*; D004032:Diet; D004195:Disease Models, Animal; D005260:Female; D006520:Hepatitis, Animal / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006527:Hepatolenticular Degeneration / Q000188:drug therapy; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000627:therapeutic use*
D008054:Lipid Peroxides; D014810:Vitamin E; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase