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

B. L. Slomiany, J. Piotrowski, A. Slomiany

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12 Scopus citations

Abstract

Aims: 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-α (TNF-α) during indomethacin-induced gastric mucosal injury. Methods: 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-α, and the measurement of caspase-3 and NOS-2 activities. Results: 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-α, 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-α, while the activity of caspase-3 decreased by 58.8% and that of NOS-2 showed a 47.3% decline. Conclusions: 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-α, NOS-2 and caspase-3.

Original languageEnglish (US)
Pages (from-to)243-253
Number of pages11
JournalInflammopharmacology
Volume6
Issue number3
DOIs
StatePublished - 1998

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Pharmacology (medical)

Keywords

  • Apoptosis
  • Caspase-3
  • Gastric mucosa
  • Indomethacin
  • Injury
  • NOS- 2
  • Sulglycotide

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