title: The effect of phosphodiesterase-5 inhibition by sildenafil citrate on inflammation and apoptosis in rat experimental colitis.
abstract: OBJECTIVE
  To investigate the effect of sildenafil citrate (SIL) on the extent of tissue integrity, oxidant-antioxidant status and apoptosis in rats with colitis.
  
  
  METHODS
  Colitis was induced by trinitrobenzenesulphonic acid (TNBS) in 40% ethanol (30 mg/ml; 0.8 ml) given intrarectally to Sprague-Dawley rats. Sildenafil (25 mg/kg/day) was administered after the induction of colitis and the treatment was continued for 7 days. Other groups received subcutaneously either N(G)-nitro- L-arginine methyl ester (l-NAME; 25 mg/kg) or N(G)-nitro-d-arginine methyl ester (d-NAME; 25 mg/kg) before SIL. After decapitation, the distal colon was scored and stored for the measurement of malondialdehyde (MDA) level, glutathione (GSH) content, myeloperoxidase (MPO) activity and apoptosis. Oxidant generation was monitored by using chemiluminescence (CL). Blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-10 assays.
  
  
  RESULTS
  The macroscopic lesion score of the colitis group was reduced by SIL (p < 0.01) and this effect was abolished by l-NAME (p < 0.01). Increase in colonic MDA along with a concomitant decrease in GSH of the colitis group was reversed by SIL (p < 0.01 and p < 0.001, respectively). l-NAME prevented the effect of SIL on GSH content (p < 0.001). Sildenafil also reduced the elevated MPO of the colitis group (p < 0.001) and this effect was reversed by L-NAME (p < 0.01). Increase in lucigenin CL and serum TNF-α levels in the colitis group were also prevented by SIL (p < 0.001 and p < 0.01, respectively).
  
  
  CONCLUSIONS
  Sildenafil is beneficial in TNBS-induced rat colitis partially by nitric oxide-dependent mechanisms via the maintenance of oxidant-antioxidant status, prevention of apoptosis, superoxide production and cytokine release.
authors.affiliation: Marmara University, Health Sciences Faculty, Department of Nursing, Istanbul, Turkey.
authors.forename: Berna
authors.initials: B
authors.lastname: Karakoyun
authors.forename: Unal
authors.initials: U
authors.lastname: Uslu
authors.forename: Feriha
authors.initials: F
authors.lastname: Ercan
authors.forename: Mehmet Serif
authors.initials: MS
authors.lastname: Aydin
authors.forename: Meral
authors.initials: M
authors.lastname: Yuksel
authors.forename: Ayliz Velioglu
authors.initials: AV
authors.lastname: Ogunc
authors.forename: Inci
authors.initials: I
authors.lastname: Alican
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005978:Glutathione / Q000032:analysis; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009195:Peroxidase / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D017382:Reactive Oxygen Species; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D000068677:Sildenafil Citrate; D009195:Peroxidase; D005978:Glutathione; D019331:NG-Nitroarginine Methyl Ester