Apoptosis of rat gastric mucosa and of primary cultures of gastric epithelial cells by indomethacin: role of inducible nitric oxide synthase and interleukin-8

In order to gain insights into indomethacin-induced gastric injury, rats we re fed with indomethacin (20 mg/kg), or alternatively, the primary cultures of rat gastric epithelial cells were cultured with different doses of indo methacin (1-1000 muM). Light microscopy, electron microscopy, fluorescence microscopy, TdT-mediated dUTP-biotin nick end labelling staining, ssDNA sta ining and DNA fragmentation assay were employed to evaluate the levels of g astric injury and apoptosis. Cells expressing inducible nitric oxide syntha se (iNOS) and interleukin (IL)-8 were localized at the rat gastric mucosa b y immunohistochemistry. Administration of indomethacin to rats caused apopt osis and injury of the gastric mucosal epithelial cells. Indomethacin also induced apoptosis of primary cultures of gastric epithelial cells in a dose -dependent manner. Cells expressing iNOS and IL-8 were detected at and arou nd the sites of gastric injury in the indomethacin-fed rats, but not in the control rats. The induction of apoptosis by indomethacin in the primary cu ltures of gastric epithelial cells suggests that the direct apoptotic capac ity of indomethacin. iNOS and IL-8 may be involved in this process.