Effect of sulglycotide on the apoptotic processes associated with indomethacin-induced gastric mucosal injury

In this study we investigated the effect of the antiulcer agent, sulglycotide, on the activity of a key pro-apoptotic protease, caspase-3, and the expression of inducible nitric oxide synthase (NOS-2) associated with gastric epithelial cell apoptosis triggered by the enhancement in tumour necrosis factor-alpha (TNF-alpha) during indomethacin-induced gastric mucosal injury.

The experiments were conducted with rats pretreated intragastrically with sulglycotide (200 mg/kg) or vehicle, followed 30 min later by an intragastric dose of indomethacin (60 mg/kg). The animals were killed 2 h later and their mucosal tissue used for macroscopic assessment, assays of epithelial cell apoptosis and TNF-alpha, and the measurement of caspase-3 and NOS-2 activities.

In the absence of sulglycotide, indomethacin caused multiple haemorrhagic lesions accompanied by a 20-fold enhancement in gastric epithelial cell apoptosis and a 47% increase in mucosal expression of TNF-alpha, while NOS-2 showed an 11.9-fold induction and the activity of caspase-3 increased 3.9-fold. Pretreatment with sulglycotide produced a 51.2% reduction in the extent of mucosal damage caused by indomethacin, a 43.9% decrease in the epithelial cell apoptosis and a 39.7% reduction in TNF-alpha, while the activity of caspase-3 decreased by 58.8% and that of NOS-2 showed a 47.3% decline.

Our findings implicate the enhanced expression of caspase-3 and NOS-2 in the process of death signalling cascade associated with indomethacin-induced gastric mucosal injury, and show that sulglycotide is capable of suppressing the pathway of apoptotic events propagated by TNF-alpha, NOS-2 and caspase-3.