Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Alanyl-glutamine (AG) is a dipeptide that fuels enterocytes and has a co-adjuvant role during gut healing. The current study aimed to investigate the potential antiulcer effect of AG in indomethacin-induced gastropathy. Gastric ulcerated rats were administered AG, AG + dexamethasone (Dexa), or pantoprazole post indomethacin exposure. Comparable to pantoprazole, AG aided gastric ulcer healing by inhibiting the proton pump and elevating the pH of gastric juice. Moreover, the dipeptide increased the serum/mucosal contents of GLP-1, pS473-Akt, and cyclin-D1. AG also abated serum TNF-Ü and gastric mucosal pS45-{uF062} catenin, pS9-GSK3{uF062}, pS133-CREB, pS536-NF-{uF06B}B, H₂O₂, claudin-1, and caspase-3. The administration of Dexa prior to AG contributed to ulcer formation and hampered AG effect on almost all the measured parameters. In conclusion, AG confers its anti-ulcerogenic/anti-secretory potentials by repressing H+-K+-ATPase pump to increase the gastric juice pH via boosting p-CREB, p-Akt, p-GSK-3Ý, and GLP-1. Moreover, it inhibits apoptosis through suppressing NF-mB/TNF-Ü/H₂O₂/claudin-1 cue. This trajectory contributes to loosen the tight junction priming AG-mediated GLP-1/Ý-catenin/cyclin-D1 that results in pronounced increase in gastric mucosa proliferation. Therefore, the crosstalk between multiple pathways orchestrates AG-mediated gastric ulcer healing

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