title: Effects of tocotrienol on tumor necrosis factor-α/d-galactosamine-induced steatohepatitis in rats.
abstract: 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.
authors.affiliation: Department of Applied Chemistry, Graduate School of Kanagawa Institute of Technology, Kanagawa 243-0292, Japan ; Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Yachi
authors.forename: Chie
authors.initials: C
authors.lastname: Muto
authors.forename: Natsuki
authors.initials: N
authors.lastname: Ohtaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Aoki
authors.forename: Taisuke
authors.initials: T
authors.lastname: Koike
authors.forename: Osamu
authors.initials: O
authors.lastname: Igarashi
authors.forename: Chikako
authors.initials: C
authors.lastname: Kiyose
keywords: fibrosis; inflammation; steatohepatitis; tocopherol; tocotrienol