Abstract
Crohn’s 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 on an experimental rat model with trinitrobenzenesulfonic acide-induced colitis. Trinitrobenzenesulfonic acid was instilled into the colon of all male Wistar rats except for those belonging to the first group. For some days, the animals in group 3 received daily sildenafil orally; the rats in group 4 received daily U-74389G intravenously, and the rats in group 5 were co-administered daily sildenafil orally and intravenous U-74389G. The rats in groups 1 and 2 were not given any treatment. During the study, the weight of the rats was recorded as a marker of their clinical condition. The colon damage was evaluated using the macroscopic colonic mucosa damage index (CMDI), microscopic (Geboes score), and biochemical methods (tissue tumour necrosis factor [TNF]-a and malondialdehyde [MDA]). Sildenafil reduced TNF-a tissue levels and increased the body weight. U-74389G reduced TNF-a, the macroscopic index of mucosal damage score (CMDI) and increased the body weight. The combined treatment with sildenafil and U-74389G reduced tissue levels of both TNF-a and MDA, lowered CMDI and microscopic Geboes score, and increased the body weight. U-74389G demonstrated a significant anti-inflammatory activity related to its ability to reduce colonic TNF-a, CMDI score, and improve weight change. We confirmed that sildenafil has an anti-inflammatory capacity in terms of reducing colonic TNF-a and improving body weight. Finally, the combined treatment showed superior effects by reducing colonic TNF-a, colonic MDA, the CMDI score, Geboes score, and by improving weight.
Published Version
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