title: A newly synthetic vitamin E derivative, E-Ant-S-GS, attenuates lung injury caused by cecal ligation and puncture-induced sepsis in rats.
abstract: BACKGROUND
  Cytokine activation and the ensuing spread of damage to distant organs play a central role in sepsis caused by generalized peritonitis, which accompanies surgical conditions such as gastrointestinal perforation. Anti-inflammatory properties have been discovered in endogenous substances such as vitamin E; we evaluated, in a rat model of peritonitis-induced sepsis, the newly synthetic vitamin E derivative E-Ant-S-GS, in which the endogenous substances vitamin E, glutathione, 5-OH-anthranilic acid, and succinic acid are chemically linked.
  
  
  METHODS
  We used a model of sepsis in male Wistar rats with the cecal ligation and puncture (CLP) method. To evaluate the anti-inflammatory effects of E-Ant-S-GS, we measured serum interleukin-6 (IL-6) levels at various times after CLP. To assess the effects of E-Ant-S-GS in acute lung injury, we evaluated histologically lung tissue 12 hours after CLP by hematoxylin-eosin staining. In addition, myeloperoxidase (MPO) activity and expression of protease-activated receptor 1 (PAR1) and high mobility group box 1 (HMGB1) in the lung were determined.
  
  
  RESULTS
  Serum IL-6 levels increased progressively after the CLP procedure; this cytokine induction was attenuated by E-Ant-S-GS. Increased MPO activity in lung tissue and marked changes in lung histology caused by CLP-induced sepsis were also ameliorated by E-Ant-S-GS. In addition, E-Ant-S-GS suppressed the upregulation of PAR1 and HMGB1 in the lungs after CLP.
  
  
  CONCLUSIONS
  The newly synthetic vitamin E derivative E-Ant-S-GS showed anti-inflammatory actions and organ-protective effects in a rat model of sepsis, suggesting its potential clinical use as a therapeutic agent against systemic inflammation.
authors: Department of Gastroenterological Surgery, Oita University Faculty of Medicine, Oita, Japan. k-yohei@oita-u.ac.jp
authors: Yohei
authors: Y
authors: Kono
authors: Masafumi
authors: M
authors: Inomata
authors: Satoshi
authors: S
authors: Hagiwara
authors: Norio
authors: N
authors: Shiraishi
authors: Takayuki
authors: T
authors: Noguchi
authors: Seigo
authors: S
authors: Kitano
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use; D002432:Cecum; D004195:Disease Models, Animal; D024243:HMGB1 Protein / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D008026:Ligation; D008297:Male; D010538:Peritonitis / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011677:Punctures; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000378:metabolism; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D015850:Interleukin-6; D044463:Receptor, PAR-1; D014810:Vitamin E; D009195:Peroxidase