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The current study aimed to investigate the possible protective effect of tadalafil and pentoxifylline (PTX) on indomethacin-induced peptic ulcers. Male albino rats were divided into five groups: control group; ulcerated group; Indomethacin + Tadalafil, in which animals were pretreated with tadalafil orally before indomethacin; Indomethacin+ PTX, in which animals were pretreated with PTX orally before indomethacin; and Indomethacin + Tadafil + PTX. Indomethacin treatment revealed histopathological changes and ulcer scoring and ulcer index were markedly increased. Serum levels of prostaglandin and heme oxygenase-1 were significantly decreased. The ulcerogenic also induced marked oxidative stress as evident from the increased malondialdehyde, decreased in gastric glutathione content and superoxide dismutase activity, while the gastric myeloperoxidase was increased. Gastric nitric oxide content was decreased and the expression of vascular endothelial growth factor was downregulated while the tumor necrosis factor \u03b1 (TNF-\u03b1) level was dramatically increased. Pretreatment of the ulcerative group by either tadalafil or PTX or their combination improved all these pathological changes. Tadalafil or PTX may have a role in protecting gastric mucosa damage caused by indomethacin which may be useful in the future for the treatment of gastric ulceration. <\/jats:p>","DOI":"10.1139\/cjpp-2020-0725","type":"journal-article","created":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T21:40:10Z","timestamp":1609882810000},"page":"864-874","update-policy":"https:\/\/doi.org\/10.1139\/csp-crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Possible protective effect of TNF-\u03b1 inhibition and triad NO\/cGMP\/VEGF activation on gastric ulcer in rats"],"prefix":"10.1139","volume":"99","author":[{"given":"Ekram Nemr","family":"Abd Al Haleem","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Al \u2013Zahraa Mohamed","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy for Girls, Al-Azhar University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sawsan Abo Bakr","family":"Zaytoon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismaelia, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam Mohamed Mohamed","family":"Arafa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"refg1\/ref1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00048.2006"},{"key":"refg2\/ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2007.10.015"},{"key":"refg3\/ref3","first-page":"160","volume":"22","author":"Ayd\u0131n K.","year":"2011","journal-title":"Eklem Hastal\u0131k Cerrahisi,"},{"key":"refg4\/ref4","unstructured":"Banchrof, J., Steven, A., and Turner, D. 1996. 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