Abstract
Purpose
Vitamin 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.
Methods
An 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.
Results
The 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).
Conclusions
Bolus 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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Acknowledgments
We would like to express our gratitude to Dr. Kazumi Ogata, who synthesized and provided the agents used in this study, and to Dr. Satoshi Hagiwara, and Dr. Takayuki Noguchi for the scientific assistance, and to Ms. Yuiko Aso, Mr. Kazune Komiya, and Ms. Kaori Sakai for their technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (ASPS) (No. 23591967).
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Hiratsuka, T., Inomata, M., Hagiwara, S. et al. Bolus injection of newly synthesized vitamin E derivative ETS-GS for the treatment of acute severe ulcerative colitis in a mouse model. Int J Colorectal Dis 28, 305–311 (2013). https://doi.org/10.1007/s00384-012-1502-y
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DOI: https://doi.org/10.1007/s00384-012-1502-y