title: Rosuvastatin reduces rat intestinal ischemia-reperfusion injury associated with the preservation of endothelial nitric oxide synthase protein.
abstract: OBJECTIVE
  To investigate the protective effect of rosuvastatin on ischemia-reperfusion (I-R)-induced small intestinal injury and inflammation in rats, and to determine the effect of this agent on the expression of endothelial nitric oxide synthase (eNOS) protein.
  
  
  METHODS
  Intestinal damage was induced in male Sprague-Dawley rats by clamping both the superior mesenteric artery and the celiac trunk for 30 min, followed by reperfusion for 60 min. Rosuvastatin dissolved in physiological saline was administered intraperitoneally 60 min before ischemia. The severity of the intestinal mucosal injury and inflammation were evaluated by several biochemical markers, as well as by histological findings. The protein levels of eNOS were determined by Western blot.
  
  
  RESULTS
  The levels of both intraluminal hemoglobin and protein, as indices of mucosal damage, were significantly increased in the I-R group compared with those in the sham-operated group. These increases, however, were significantly inhibited by treatment with rosuvastatin in a dose-dependent manner. The protective effects of rosuvastatin were also confirmed by histological findings. Exposure of the small intestine to I-R resulted in mucosal inflammation characterized by significant increases in thiobarbituric acid-reactive substances, tissue-associated myeloperoxidase activity, and the mucosal contents of rat cytokine-induced neutrophil chemoattractant-1 (CINC-1) and tumor necrosis factor-alpha (TNF-alpha). These increases in inflammatory parameters after I-R were significantly inhibited by pretreatment with rosuvastatin at a dose of 10 mg/kg. Furthermore, mRNA expression of CINC-1 and TNF-alpha was increased after I-R, and this increase was also inhibited by rosuvastatin. The mucosal protein levels of eNOS decreased during I-R, but were preserved in rats treated with rosuvastatin.
  
  
  CONCLUSIONS
  Rosuvastatin inhibits rat intestinal injury and inflammation induced by I-R, and its protection is associated with the preservation of eNOS protein.
authors.affiliation: Department of Medical Proteomics, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kyoto 602-8566, Japan. ynaito@koto.kpu-m.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Naito
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Katada
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Takagi
authors.forename: Hisato
authors.initials: H
authors.lastname: Tsuboi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kuroda
authors.forename: Osamu
authors.initials: O
authors.lastname: Handa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kokura
authors.forename: Norimasa
authors.initials: N
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ichikawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000235:genetics; D005464:Fluorobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000032:analysis*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D012333:RNA, Messenger; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000068718:Rosuvastatin Calcium; D052250:Nitric Oxide Synthase Type III