['Caspases, a class of cysteine proteases, modulate apoptosis. Nitric oxide (NO)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) are a new class of NSAID derivatives with reduced gastrointestinal toxicity. The aim of this study was to investigate whether cysteine endoproteases are involved in the pathogenesis of NSAID gastropathy and are target for NO-aspirin (NCX-4016).', "Rats were treated orally with aspirin or equimolar doses of NCX-4016. Caspase activities were measured by fluorometric assay. Apoptosis was quantified by an enzyme-linked immunosorbent assay for histone-associated DNA, DNA ladder on agarose gel, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. A primary culture of gastric chief cells was used to investigate whether NCX-4016 modulates guanosine 3',5'-cyclic monophosphate (cGMP)-dependent pathways.", 'Short- and long-term (7 days) aspirin administration resulted in a time- and dose-dependent gastric injury that was associated with apoptosis and caspase up-regulation. Z-VAD.FMK, a pancaspase inhibitor, and NO donors protected from acute damage induced by aspirin. NCX-4016 spared the gastric mucosa and caused caspase inactivation by S-nitrosylation. Inhibition of tumor necrosis factor (TNF)-alpha release or activity by TAPI-2 or anti-TNF-alpha receptor monoclonal antibodies protected against mucosal damage and caspase activation. NCX-4016 protected gastric chief cells from toxicity induced by TNF-alpha by activating cGMP-dependent pathways.'] Is gastrointestinal safety of nitric oxide-derived aspirin related to inhibition of ICE-like cysteine proteases in rats?