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A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND\u2010induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague\u2010Dawley rats through gastric gavage of IND. Following an 18\u2010hour fast, IND was administered to experimental rats. They were sacrificed at 3\u2010, 6\u2010 and 12\u2010hour intervals. Parietal cells (H<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase \u03b2\u2010subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis\u2010signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti\u2013phospho\u2010histone H2A.X) and autophagy (MAP\u2010LC3, LAMP\u20101 and cathepsin B)\u2010related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time\u2010dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP\u2010LC3\u2010II, LAMP\u20101 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time\u2010dependent apoptotic and autophagic cell death of PCs. Our study provides the first indication of the interactions between these two homeostatic pathways in this context.<\/jats:p>","DOI":"10.1111\/iep.12370","type":"journal-article","created":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T13:35:27Z","timestamp":1601300127000},"page":"230-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis\u2010 and autophagy\u2010associated molecules"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8679-4897","authenticated-orcid":false,"given":"Sahar M.","family":"Gebril","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology Osaka Medical College Osaka Japan"},{"name":"Department of Histology Faculty of Medicine Sohag University Sohag Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Osaka Medical College Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masa\u2010Aki","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Osaka Medical College Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Maemura","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology Osaka Medical College Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-9328","authenticated-orcid":false,"given":"Eman E.","family":"Abu\u2010Dief","sequence":"additional","affiliation":[{"name":"Department of Histology Faculty of Medicine Sohag University Sohag Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-2211","authenticated-orcid":false,"given":"Mahmoud R. 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