• Int J Colorectal Dis · Mar 2013

    Bolus injection of newly synthesized vitamin E derivative ETS-GS for the treatment of acute severe ulcerative colitis in a mouse model. New vitamin E derivative for acute severe UC.

    • Takahiro Hiratsuka, Masafumi Inomata, Satoshi Hagiwara, Yohei Kono, Norio Shiraishi, Takayuki Noguchi, and Seigo Kitano.
    • Department of Gastroenterological Surgery, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-city, Oita 879-5593, Japan. htakahiru@oita-u.ac.jp
    • Int J Colorectal Dis. 2013 Mar 1; 28 (3): 305-11.

    PurposeVitamin E with its antioxidant action has therapeutic effects on ulcerative colitis (UC), but use of vitamin E is limited because of its insolubility in water. We developed ETS-GS (γ-L-glutamyl-S-[2-[[[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltri-decyl)-2 H-1-benzopyran-6-yl]oxy]carbonyl]-3-oxo-3-[(2-sulfoethyl)amino]propyl]-L-cysteinylglycine sodium salt), a newly synthesized soluble vitamin E derivative with strong antioxidant action. We evaluated the therapeutic effects of bolus injection of ETS-GS on acute severe UC in a mouse model.MethodsAn animal model of acute severe UC was induced by feeding mice 5 % dextran sulfate sodium (DSS) for 5 days, followed by 1 % DSS on days 5-8, the experimental period. ETS-GS or saline was administered by subcutaneous bolus injection during the experimental period. We examined disease activity index (DAI) score, histological score, colon length, colon weight, and serum cytokines in the mice.ResultsThe following results at day 8 in the DSS + ETS-GS group were significantly lower than those in the DSS + Saline group: DAI score, 2.6 ± 0.6 vs. 3.1 ± 0.5; histological score, 2.1 ± 1.0 vs. 3.1 ± 0.8; serum interleukin (IL)-6, 15 ± 9.4 vs. 39 ± 23 pg/ml; and keratinocyte-derived chemokine (KC), 122 ± 61 vs. 228 ± 66 pg/ml (P < 0.05). Colon length, colon weight, and serum IL-10 in the DSS + ETS-GS group were significantly higher than those in the DSS + Saline group (88 ± 12 vs. 75 ± 5.7 mm, 0.48 ± 0.09 vs. 0.38 ± 0.05 g, and 55 ± 18 vs. 31 ± 10 pg/ml, respectively; P < 0.05).ConclusionsBolus injection of ETS-GS may be one therapeutic modality for acute severe UC. Its effects are associated with suppression of serum IL-6 and serum KC and promotion of serum IL-10.

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