α-Tocopherol deficiency fails to aggravate toxic liver injury but liver injury causes α-tocopherol retention

Abstract

The possible aggravation of liver injury by impaired cellular antioxidant function was investigated. A vitamin E-deficient diet (0.5 mg/kg α-tocopherol; control 100 mg/kg) significantly reduced rat liver α-tocopherol concentrations after 4 weeks (1.8 ± 1.7 μg/g; control 34.4 ± 2.4 μg/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 α-tocopherol content followed administration of GalN or CCl4 in both normocupric and copper-laden E(−) rats. Thus α-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 α-tocopherol after liver damage may partly explain low serum vitamin E levels seen in clinical liver disease.