title: Effectiveness of sildenafil and U-74389G in a rat model of colitis.
abstract: BACKGROUND
  Crohn disease is still incurable. Compounds with anti-inflammatory and/or antioxidative effects are tested in various preclinical models of the disease. Our aim was to investigate the effects of sildenafil and lazaroid U-74389G in an experimental rat model of trinitrobenzenesulfonic acid-induced colitis.
  
  
  METHODS
  Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for the rats belonging to the first group. For 6 days, the animals in group 3 were administered daily sildenafil orally, the rats in group 4 were administered daily U-74389G intravenously, and the rats in group 5 were coadministered daily sildenafil orally and intravenous U-74389G. The rats in groups 1 and 2 were not administered any treatment. During the study, the weights were recorded as a marker of clinical condition. The colon damage was evaluated using macroscopic colon mucosal damage index (CMDI), microscopic (Geboes score), and biochemical methods (tissue tumor necrosis factor [TNF]-α and malondialdehyde [MDA]).
  
  
  RESULTS
  Sildenafil reduced TNF-α tissue levels and increased body weight. U-74389G reduced TNF-α, the macroscopic index of mucosal damage score (CMDI) and increased body weight. The combined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-α and MDA, lowered CMDI and microscopic Geboes score, and increased body weight.
  
  
  CONCLUSIONS
  U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reduce colonic TNF-α, CMDI score, and improve weight change. We confirmed that sildenafil has anti-inflammatory capacity by reducing colonic TNF-α and by improving body weight. Finally, the combined treatment showed superior effects by reducing colonic TNF-α, colonic MDA, CMDI score, Geboes score, and by improving weight.
authors.affiliation: 1st Department of Propaedeutic Surgery, Hippokrateio Hospital, School of Medicine, University of Athens, Athens, Greece. Electronic address: antonis.margonis@gmail.com.
authors.forename: Georgios Antonios
authors.initials: GA
authors.lastname: Margonis
authors.affiliation: 1st Department of Propaedeutic Surgery, Hippokrateio Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Christoloukas
authors.affiliation: 2nd Department of Propaedeutic Surgery, Laiko Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Efstathios
authors.initials: E
authors.lastname: Antoniou
authors.affiliation: 4th Department of Surgery, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Arkadopoulos
authors.affiliation: 1st Department of Propaedeutic Surgery, Hippokrateio Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Theodoropoulos
authors.affiliation: 1st Department of Pathology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Agrogiannis
authors.affiliation: 1st Department of Surgery, Laiko Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Pikoulis
authors.affiliation: 1st Department of Pathology, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Efstratios S
authors.initials: ES
authors.lastname: Patsouris
authors.affiliation: 1st Department of Propaedeutic Surgery, Hippokrateio Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: George C
authors.initials: GC
authors.lastname: Zografos
authors.affiliation: Experimental-Research Center, Elpen Pharmaceuticals, Athens, Greece.
authors.forename: Apostolos E
authors.initials: AE
authors.lastname: Papalois
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011281:Pregnatrienes / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D011897:Random Allocation; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000975:Antioxidants; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011281:Pregnatrienes; D011687:Purines; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C074965:U 74389F; D008315:Malondialdehyde; D014302:Trinitrobenzenesulfonic Acid; D000068677:Sildenafil Citrate
keywords: Lazaroid U-74389G; MDA; Sildenafil; TNBS-induced colitis; TNF-α