Is inducible nitric oxide synthase (iNOS) involved in the pathogenesis of indomethacin-induced intestinal damage?

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

“…Thus, the protective action of sulglycotide can be safely achieved even in the presence of agents known to inhibit prostaglandin synthesis [4,5,10]. Moreover, recent data point towards detrimental effects of NSAIDs on processes linked to cell-cycle progression, induction of proinflammatory cytokine TNF-~ expression, disturbances in nitric oxide, and apoptosis [10,15,16,18,19]. The amplification and propagation of the cell death signalling cascade induced by TNF-~ involve the activation of a family of specific cysteine proteases, known as caspases, that are under the regulatory control of nitric oxide [20,23,[29][30][31].…”

“…Although the damaging effects of NSAIDs are most often ascribed to the impairment in prostaglandin synthesis and the disturbances in mucosal blood flow and superoxide radical generation [11][12][13], more recent data point to a detrimental action of these drugs on processes associated with cellular proliferation, cellcycle progression and apoptosis [10,[14][15][16]. Other recently recognized cytotoxic effects of NSAIDs are triggered by an increase in mucosal generation of proinflammatory cytokines and disturbances in the nitric oxide signalling pathway [15,[17][18][19].…”