Alanyl-glutamine heals indomethacin induced gastric ulceration in rats via anti-secretory and anti-apoptotic mechanisms.

Abstract

OBJECTIVES 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 ulcer-healing effect of AG in indomethacin-induced gastropathy. METHODS Animals (n = 10 rats/group) were randomly allocated into 5 groups. Gastric ulcerated rats were administered AG, AG + dexamethasone (DEXA), or pantoprazole post indomethacin exposure. RESULTS Comparable to pantoprazole, AG inhibited H-KATPase pump and elevated the pH of gastric juice. Moreover, the dipeptide increased the serum/mucosal contents of GLP-1, pS473-Akt, and cyclin-D1. On the other hand, AG abated serum TNF-α and gastric mucosal content of pS45-β catenin, pS9-GSK3β, pS133-CREB, pS536-NF-κB, H2O2, claudin-1, and caspase-3. The administration of DEXA prior to AG hampered its effect on almost all the measured parameters. CONCLUSIONS AG confers its anti-ulcerogenic/anti-secretory potentials by repressing the proton pump to increase the gastric juice pH via boosting p-CREB, p-Akt, p-GSK-3β, and GLP-1. Also, it inhibits apoptosis through suppressing NF-κB/TNF-α/H2O2/claudin-1 cue. This trajectory contributes to loosen the tight junction priming AG-mediated GLP-1/β-catenin/cyclin-D1 that results in pronounced increase in gastric mucosa proliferation. Therefore, the crosstalk between multiple pathways orchestrates the action of AG against gastric ulceration.