title: Effect of cilostazol, a selective type-III phosphodiesterase inhibitor, on water-immersion stress-induced gastric mucosal injury in rats.
abstract: BACKGROUND
  Cilostazol, a specific type-III phosphodiesterase inhibitor, is widely used for the treatment of ischemic symptoms of peripheral vascular disease. Recent studies have reported that the mechanism of cilostazol is related to the suppression of pro-inflammatory cytokine production and improvement of local microcirculation disturbances. The pathogenesis of stress-induced gastric mucosal lesions is characterized by the activation of inflammatory cells and the production of inflammatory cytokines. The effects of cilostazol on the development of gastric mucosal lesions have not been reported. In the present study, we examined the effect of a cilostazol on water-immersion stress-induced gastric mucosal lesions.
  
  
  METHODS
  Rats were subjected to water-immersion stress with or without pretreatment with a single intraperitoneal injection of the selective type-III phosphodiesterase inhibitor, cilostazol. We measured the gastric mucosal lesion and the concentrations of myeloperoxidase (MPO), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), as an index of neutrophil accumulation and pro-inflammatory cytokine production.
  
  
  RESULTS
  Cilostazol ameliorated the gastric mucosal injury induced by water-immersion stress (P<0.001). The gastric contents of MPO, TNF-alpha, IL-1beta, and CRO/CINC-1 were all increased after water-immersion stress and were reduced to almost normal levels by cilostazol.
  
  
  CONCLUSIONS
  In this study, we demonstrated that a selective type-III phosphodiesterase inhibitor, cilostazol, inhibited stress-induced gastric inflammation and damage via suppressing the production of pro-inflammatory cytokines. Cilostazol may be useful for preventing gastric mucosal lesions.
authors.affiliation: Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Ohba
authors.forename: Michiro
authors.initials: M
authors.lastname: Otaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Odashima
authors.forename: Mario
authors.initials: M
authors.lastname: Jin
authors.forename: Koga
authors.initials: K
authors.lastname: Komatsu
authors.forename: Noriaki
authors.initials: N
authors.lastname: Konishi
authors.forename: Isao
authors.initials: I
authors.lastname: Wada
authors.forename: Youhei
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Matsuhashi
authors.forename: Jinko
authors.initials: J
authors.lastname: Oyake
authors.forename: Natsumi
authors.initials: N
authors.lastname: Hatakeyama
authors.forename: Sumio
authors.initials: S
authors.lastname: Watanabe
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism; D000077407:Cilostazol; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007101:Immersion / Q000009:adverse effects; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D013315:Stress, Psychological; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
chemical_list: D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D007375:Interleukin-1; D010726:Phosphodiesterase Inhibitors; D013777:Tetrazoles; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D000077407:Cilostazol