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The protective potential of carbon monoxide (CO) in several inflammatory disorders has been clarified. The goal of the current study was to investigate the gastroprotective effect of CO produced by its pharmacological donor (CORM2) and its nanoparticles (NPs) against indomethacin (INDO)-induced ulcers. Investigations on CORM2's dose-dependent effects were also conducted. For induction of gastric ulcer, 100\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup> of INDO was given orally. Before ulcer induction, CORM2 (5, 10, and 15\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>), CORM2 nanoparticles (5\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>), or ranitidine (30\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) were given intraperitoneally for 7\u00a0days. Ulcer score, gastric acidity, gastric contents of malondialdehyde (MDA), nitric oxide (NO), heme oxygenase-1 (HO-1), and carboxyhemoglobin (COHb) blood content were estimated. Additionally, gene expression of nuclear factor erythroid 2-related factor 2 (NRF2) and immunohistochemical staining of cyclooxygenase-1 (COX-1) as well as cyclooxygenase-2 (COX-2) were analyzed. Results demonstrated a substantial dose-dependent decrease in ulcer score, pro-inflammatory indicators, and oxidative stress markers with CORM2 and its NPs. Furthermore, CORM2 and its NPs markedly increased NRF2, COX-1, and HO-1, but CORM2 NPs outperformed CORM2 in this regard. In conclusion, the CO released by CORM2 can protect against INDO-induced gastric ulcers dose dependently, and the highest used dose had no effect on COHb concentration.\n<\/jats:p>","DOI":"10.1007\/s10787-023-01166-4","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:02:37Z","timestamp":1680739357000},"page":"1495-1510","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potential effects of carbon monoxide donor and its nanoparticles on experimentally induced gastric ulcer in rats"],"prefix":"10.1007","volume":"31","author":[{"given":"Alaa E.","family":"Elsisi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3780-673X","authenticated-orcid":false,"given":"Esraa F.","family":"Mekky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally E.","family":"Abu-Risha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"issue":"22","key":"1166_CR1","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.4155\/fmc-2018-0152","volume":"10","author":"AM Abdellah","year":"2018","unstructured":"Abdellah AM, Sliem MA, Bakr M, Amin RM (2018) Green synthesis and biological activity of silver-curcumin nanoconjugates. 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