It has been reported that α-
tocopherol (α-Toc), a
vitamin E analog, is effective for treatment of non-
alcoholic steatohepatitis (NASH). However, it is unknown whether or not other
vitamin E analogs are effective. Therefore we designed a new rat model of
steatohepatitis induced by
tumor necrosis factor-α (TNF-α) stimulation, and used it to investigate the effects of
vitamin E analogs. The rat liver
triglyceride content increased with the dosage of TNF-α/d-
galactosamine (GalN), but was suppressed by intake of both
tocotrienol (T3) and α-
tocopherol. Moreover,
lipid peroxides (
thiobarbituric acid-reactive substances) level in the liver level was also lower in both groups after
tocotrienol and α-Toc intake. Intake of both
tocotrienol and α-
tocopherol also tended to control the increase of liver damage marker activity. In the
tocotrienol and α-
tocopherol groups, increases of inflammatory
cytokines mRNA expression in the liver were inhibited, and these effects were considered to contribute to improvement of
inflammation and
fibrosis. The expression of mRNAs for inflammatory
cytokines in rat primary hepatocytes was increased by TNF-α stimulation, but was inhibited by addition of α-
tocotrienol and γ-
tocotrienol. Transforming growth factor-β1
mRNA expression in particular was significantly inhibited by γ-
tocotrienol. These findings suggest that
tocotrienol species are effective for amelioration of
steatohepatitis, and that
tocotrienol and α-
tocopherol exert a synergistic effect.