title: 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.
abstract: OBJECTIVE
  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.
authors: 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
authors: Takahiro
authors: T
authors: Hiratsuka
authors: Masafumi
authors: M
authors: Inomata
authors: Satoshi
authors: S
authors: Hagiwara
authors: Yohei
authors: Y
authors: Kono
authors: Norio
authors: N
authors: Shiraishi
authors: Takayuki
authors: T
authors: Noguchi
authors: Seigo
authors: S
authors: Kitano
mesh_terms: D000818:Animals; D018925:Chemokines / Q000097:blood; D003093:Colitis, Ulcerative / Q000097:blood / Q000188:drug therapy* / Q000473:pathology*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000097:blood; D007267:Injections; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D018925:Chemokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D009842:Oligopeptides; C568419:gamma-L-glutamyl-S-(2-(((3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12- trimethyltridecyl)-2H-1-benzopyran-6-yl)oxy)carbonyl)-3-oxo-3-((2-sulfoethyl)amino)propyl)-L-cysteinylglycine sodium salt; D016753:Interleukin-10; D014810:Vitamin E; C074302:keratinocyte-derived chemokines