title: Role of Rosiglitazone as a Gastroprotective Agent Against Indomethacin-Induced Gastric Mucosal Injury in Rats.
abstract: BACKGROUND
  Rosiglitazone, an insulin sensitizing agent, has been recently implicated in the control of inflammatory processes and modulation of expression of various cytokines such as tumor necrosis factor (TNF-α). However, its mechanistic effect of gastric mucosal integrity remains to be elucidated.
  
  
  METHODS
  The present study was designed to determine effect of rosiglitazone on gastric mucosal lesions induced by indomethacin (IND) in rats. Pyloric ligation was performed for the collection of gastric juice, and gastric ulceration was induced by a single intraperitoneal injection of IND (30 mg/kg).
  
  
  RESULTS
  IND administration caused a significant decrease in the volume of gastric juice mucin and gastric mucosal nitrite and prostaglandin E2(PGE2) levels. This was accompanied by a significant increase in gastric juice free and total acidity and pepsin activity. In addition, an elevation in the gastric mucosal lipid peroxide and serum TNF-α level was observed. Pretreatment with rosiglitazone (10 mg/kg, orally, for 1 weeks) resulted in a significant reduction in the elevated gastric mucosal lesions and lipid peroxides levels. This was associated with a marked increase in gastric juice mucin and a reduction in TNF-α level. Moreover, rosiglitazone significantly increased the gastric mucosal total nitrite and PGE2levels.
  
  
  CONCLUSIONS
  Rosiglitazone exerts a gastroprotective effect against IND-induced gastric mucosal lesions and its anti-ulcer effect is mediated via scavenging free radicals, increasing NO, PGE2and mucus production in addition to its anti-inflammatory mechanisms. Thus, rosiglitazone could be a relevant drug for patients taking non-steroidal anti-inflammatory drugs (NSAIDs) and at high risk of developing gastric ulceration.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, Egypt.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Taye
authors.affiliation: Department of physiology, Faculty of Medicine, Minia University, Egypt.
authors.forename: Adel H
authors.initials: AH
authors.lastname: Saad
keywords: Gastric ulcer; Indomethacin; Lipid peroxides; Nitric oxide; Rosiglitazone; TNF-α