Alpha-tocopherol deficiency fails to aggravate toxic liver injury but liver injury causes alpha-tocopherol retention.
The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg alpha-tocopherol; control 100 mg/kg) significantly reduced rat liver alpha-tocopherol concentrations after 4 weeks (1.8 +/- 1.7 micrograms/g; control 34.4 +/- 2.4 micrograms/g, p < 0.001). The effects of copper loading (Cu, 3 g/kg diet); galactosamine (GalN, 0.85 g/kg i.p.); or carbon tetrachloride (CCl4, 10 mmol/kg i.p.) were examined. Serum aspartate transaminase activity was elevated slightly by vitamin E deficiency but not by hepatic copper accumulation. In vitamin E-replete (E+) and vitamin E-deficient (E-) rats, GalN or CCl4 caused a large and comparable elevation in serum AST and OCT activity. This effect on AST was markedly reduced by copper loading in vitamin E replete (E+) rats, but in E(-) rats copper had significantly less protective effect. Copper also diminished the OCT response to GalN in E+, though not E-, rats. A significant rise in total hepatic alpha-tocopherol content followed administration of GalN or CCl4 in both normocupric and copper-laden E(-) rats. Thus alpha-tocopherol deficiency (a) was not hepatotoxic per se; (b) failed to potentiate the toxicity of copper, GalN or CCL4; but (c) partially abolished the protection by copper against toxin-induced liver injury. Retention of hepatic alpha-tocopherol after liver damage may partly explain low serum vitamin E levels seen in clinical liver disease.
Barrow
L
L
Department of Child Health, University of Leicester, United Kingdom.
Patel
H R
HR
Tanner
M S
MS
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D008297:Male; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000378:metabolism*; D014811:Vitamin E Deficiency / Q000150:complications* / Q000201:enzymology
D014810:Vitamin E; C022345:4-phenylenediamine oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors