Objective: 

Glucagon-like peptide-2 (GLP-2) is a proglucagon-derived peptide hormone acting as a specific gastrointestinal growth factor. Teduglutide is a dipeptidylpeptidase IV-resistant synthetic analogue of human GLP-2. Blocking the synthesis of protective proteins through a transcriptional inhibitor such as actinomycin D (Act D) sensitizes many cell types to TNF-alpha toxicity. In this study, we aimed to investigate whether teduglutide has effects on gastric mucosal morphology and oxidative stress at gastric injury induced by TNF-alpha/Act D in mice.

Methods: 

The gastric injury was induced by intraperitoneal administration of 15 mg/kg TNF-alpha and 800 mg/kg Act D per mouse. Animals were injected subcutaneously 200 mg/kg teduglutide every 12 hr for 10 consecutive days prior to the administration of TNF-alpha and Act D. Samples from the fundic stomach were fixed in Bouin's solution and embedded in paraffin for light microscopic examination. The sections 5 mm in thickness were stained with hematoxylin-eosin. Stomach tissue was homogenized in 0.9% saline to make up to 10% homogenate. Glutathione (GSH) and lipid peroxidation (LPO) levels and lactate dehydrogenase (LDH) activity were examined in these homogenates by spectrophotometry.

Results: 

Administration of TNF-alpha/Act D to mice caused degenerative morphological changes on gastric mucosal architecture. The stomach GSH levels were significantly decreased, while LPO and LDH activities were significantly increased in the TNF-alpha/Act D group as compared with control group. Teduglutide administration to TNF-alpha/Act D group reduced the damage in the gastric mucosa, and reversed these biochemical effects.

Conclusions: 

These results suggest that teduglutide pretreatment may prevent TNF-alpha/Act D-induced gastric injury in mice.