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Alanyl-glutamine Heals Indomethacin-induced Gastric Ulceration in Rats Via Antisecretory and Anti-apoptotic Mechanisms

El-Lekawy, Ahmed M.*; Abdallah, Dalaal M.; El-Abhar, Hanan S.

Journal of Pediatric Gastroenterology and Nutrition: December 2019 - Volume 69 - Issue 6 - p 710–718
doi: 10.1097/MPG.0000000000002474
Original Articles: Nutrition
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Objectives: Alanylglutamine (AG) is a dipeptide that fuels enterocytes and has a coadjuvant 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, or pantoprazole after indomethacin exposure.

Results: Comparable to pantoprazole, AG inhibited H+-K+ATPase pump, and elevated the pH of gastric juice. Moreover, the dipeptide increased the serum/mucosal contents of glucagon-like peptide-1 (GLP-1), pS473-Akt, and cyclin-D1. On the contrary, AG abated serum tumor necrosis factor-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 dexamethasone before AG hampered its effect on almost all the measured parameters.

Conclusions: AG confers its antiulcerogenic/antisecretory 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 nuclear factor-kappa B/tumor necrosis factor-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.

*Total Parenteral Nutrition Department, New kasr Al-Aini Teaching Hospital

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Address correspondence and reprint requests to Ahmed M. El-Lekawy, MSc, Clinical Pharmacist, Total Parenteral Nutrition Department, New Kasr Al-Aini Teaching Hospital, Kasr Al-Aini St, Cairo, 11562, Egypt (e-mail: Ahmedpharma1990@gmail.com).

Received 27 May, 2019

Accepted 8 August, 2019

The authors report no conflicts of interest.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,