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- W329818892 abstract "Apoptosis is the process of programmed cell death characterized by a series of distinct biochemical and morphological changes which involve activation of caspase proteases cascade that remains under the regulatory control of nitric oxide. Here, we investigated the activity of a key apoptotic protease, caspase-3, and the expression of inducible nitric oxide synthase (NOS-2) and tumor necrosis factor-alpha (TNF-alpha) associated with gastric epithelial cells apoptosis during indomethacin-induced gastric mucosal injury, and evaluated the effect of antiulcer agent sucralfate on this process.The experiments were conducted with groups of rats pretreated intragastrically with 200 mg/kg sucralfate or the vehicle, followed 30 min later by an intragastric dose of indomethacin at 60 mg/kg. The animals were killed 2 h later and their gastric mucosal tissue used for macroscopic assessment, assays of epithelial cells apoptosis and TNF-alpha, and the measurements of caspase-3 and NOS-2 activities.In the absence of sucralfate, indomethacin caused multiple hemorrhagic lesions occupying 29.3 mm2 of the corpus area, and accompanied by a 20-fold enhancement in gastric epithelial cells 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 sucralfate produced a 59.7% reduction in the extent of mucosal damage caused by indomethacin, a 41.2% decrease in the epithelial cells apoptosis and a 33.4% reduction in TNF-alpha, while the activity of caspase-3 decreased by 45% and that of NOS-2 showed a 44.7% decline.The results implicate caspase-3 in the process of indomethacin-induced gastric epithelial cells apoptosis, and point towards participation of NOS-2 in the amplification of the cell death signaling cascade. Our findings also show that sucralfate protection against gastric mucosal injury caused by indomethacin involves the suppression of NOS-2 and the apoptotic events propagated by caspase-3." @default.
- W329818892 created "2016-06-24" @default.
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- W329818892 date "1999-03-01" @default.
- W329818892 modified "2023-10-18" @default.
- W329818892 title "Role of caspase-3 and nitric oxide synthase-2 in gastric mucosal injury induced by indomethacin: effect of sucralfate." @default.
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