title: Sildenafil citrate protects against gastric mucosal damage induced by indomethacin in rats.
abstract: OBJECTIVE
  The present study was conducted to investigate the possible gastroprotective effect of sildenafil citrate, a selective inhibitor of cyclic guanosine monophosphate-specific phosphodiesterase, against indomethacin-induced gastric damage in rats. Further, the study was extended to investigate some possible mechanisms underlying this effect.
  
  
  METHODS
  Forty rats were assigned to vehicle (saline), control (indomethacin, 30 mg/kg, p.o.), ranitidine (50 mg/kg, p.o.), sildenafil (5 mg/kg, p.o.) and sildenafil (10 mg/kg, p.o.); the drugs were administered 30 minutes prior to indomethacin. Four hours after indomethacin administration, all rats were sacrificed and the gastric juices were collected. Then, each stomach was opened and macroscopically examined for gastric lesions and longitudinal sections were used for biochemical and histopathological analysis.
  
  
  RESULTS
  Our results indicated that indome-thacin induced marked ulceration in the gastric mucosa, in addition to an increase in gastric acidity as compared to saline group (p ≤ 0.05). Furthermore, indomethacin group showed lower concentration of mucin and reduced glutathione, whereas, lipid peroxides and tumor necrosis factor-α (TNF-α) were elevated in the stomach homogenate. Pretreatment with sildenafil (5 mg/kg) significantly reduced gastric acid secretion, ulcer score and lipid peroxides production without effect on mucin, TNF-α, or nitric oxide (NO). The higher dose of sildenafil (10 mg/kg) provided similar results with the exception of increasing tissue NO (p ≤ 0.05).
  
  
  CONCLUSIONS
  We concluded that sildenafil can protect the gastric mucosa against the aggressive effect of indomethacin via increasing NO and inhibiting lipid peroxidation. Therefore, sildenafil might be helpful in preventing the gastric adverse effects of non-steroidal anti-inflammatory drugs in a clinical setting.
authors: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
authors: Y M
authors: YM
authors: Moustafa
authors: D M
authors: DM
authors: Khoder
authors: E E
authors: EE
authors: El-Awady
authors: S A
authors: SA
authors: Zaitone
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000502:physiology; D005753:Gastric Mucosa / Q000187:drug effects*; D007213:Indomethacin / Q000633:toxicity*; D054086:KATP Channels / Q000502:physiology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D054086:KATP Channels; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D006152:Cyclic GMP; D007213:Indomethacin