Effectiveness of sildenafil and U-74389G in a rat model of colitis

J Surg Res. 2015 Feb;193(2):667-74. doi: 10.1016/j.jss.2014.08.064. Epub 2014 Sep 6.


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.

Materials and 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.

Keywords: Lazaroid U-74389G; MDA; Sildenafil; TNBS-induced colitis; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / therapeutic use*
  • Colitis / chemically induced
  • Colitis / drug therapy*
  • Colitis / pathology
  • Colon / metabolism
  • Colon / pathology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Male
  • Malondialdehyde / metabolism
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Piperazines / therapeutic use*
  • Pregnatrienes / therapeutic use*
  • Purines / therapeutic use
  • Random Allocation
  • Rats, Wistar
  • Sildenafil Citrate
  • Sulfones / therapeutic use*
  • Trinitrobenzenesulfonic Acid
  • Tumor Necrosis Factor-alpha / metabolism


  • Antioxidants
  • Phosphodiesterase 5 Inhibitors
  • Piperazines
  • Pregnatrienes
  • Purines
  • Sulfones
  • Tumor Necrosis Factor-alpha
  • U 74389F
  • Malondialdehyde
  • Trinitrobenzenesulfonic Acid
  • Sildenafil Citrate