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Rats were assigned into six random groups: diseased group (AA), injected once with 2\u00a0ml acetic acid (3%) intrarectally, 2\u00a0days before sacrification. SILD\u2009+\u2009AA, received sildenafil (25\u00a0mg\/kg, orally) for 6\u00a0days starting 3\u00a0days pre-injection of AA; SILD-t\u2009+\u2009AA, received sildenafil (25\u00a0mg\/kg, orally), starting at time of AA injection and continued for 3\u00a0days; DEXA\u2009+\u2009AA, received dexamethasone (2\u00a0mg\/kg, i.p.) for 3\u00a0days, starting at time of AA injection; SILD-t\u2009+\u2009DEXA\u2009+\u2009AA, received sildenafil (25\u00a0mg\/kg, orally) and dexamethasone (2\u00a0mg\/kg, i.p.), as mentioned. Sildenafil markedly ameliorated disease activity index (DAI), ulcer scores, colon length shortening and colonic histopathological changes. Mechanistically, Sildenafil markedly attenuated immunoexpression of NF-\u03baB p65\/ TNF-\u03b1 and COX-2, diminished oxidative stress (\u2193 MDA\/NO levels and \u2191 GSH level and SOD activity), increased levels of Nrf-2\/HO-1, compared to untreated group. Taken together, Sildenafil treatment suppressed acetic acid-induced ulcerative colitis, probably via inhibiting NF-\u03baB\/TNF-\u03b1 signaling dependent of Nrf-2\/HO-1 pathway, reducing oxidative stress and attenuating inflammation. Surprisingly, effects of sildenafil were unpromoted in a time dependant manner. Short term treatment with sildenafil was sufficient to exert its coloprotective effect, while longer term pretreatment was only superior among other treatments in the macroscopical changes. Moreover, concurrent administration of sildenafil and dexamethasone had the preference in boosting the antioxidant defense and anti-inflammatory mechanisms, visualized by histopathological\/immunohistochemical changes.<\/jats:p>","DOI":"10.1007\/s10787-022-01016-9","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T13:03:44Z","timestamp":1657803824000},"page":"1351-1362","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The emerging coloprotective effect of sildenafil against ulcerative colitis in rats via exerting counterbalance between NF-\u03baB signaling and Nrf-2\/HO-1 pathway"],"prefix":"10.1007","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0281-1646","authenticated-orcid":false,"given":"Ghada S.","family":"El-Tanbouly","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5140-1774","authenticated-orcid":false,"given":"Rehab S.","family":"Abdelrahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"1016_CR1","doi-asserted-by":"crossref","unstructured":"Abdelrahman RS, N. 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