Possible Protective Effect of TNF-α Inhibition and Triad NO/cGMP/VEGF Activation on Gastric Ulcer in Rats

A peptic ulcer is one of the world's major gastrointestinal disorders, embracing both gastric and duodenal ulcers, and affecting 10% of the world population. The current study aimed to investigate the possible protective effect of tadalafil and pentoxifylline 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. Indomethacin + combination of two drugs. Indomethacin revealed histopathological changes, ulcer scoring, and ulcer index were markedly increased. Serum levels of PGE2 and HO-1 were significantly decreased. The ulcerogenic also induced marked oxidative stress as evident from the increased MDA, decreased in gastric GSH content and SOD activity, while the gastric MPO was increased. Gastric NO content was decreased and the expression of VEGF was downregulated while the TNF-a level was dramatically increased. Pretreatment of the ulcerative group by either tadalafil or pentoxifylline 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.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author