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We investigated whether <jats:sc>l<\/jats:sc>\u2010arginine could protect against age\u2010related gastric ulceration induced by indomethacin. Aged and adult male Wistar rats were administered sole and combined treatment of\u00a0\n<jats:sc>l<\/jats:sc>\u2010arginine and\u00a0<jats:italic>N<\/jats:italic><jats:sub>\u03c9<\/jats:sub>\u2010nitro\u2010l\u2010arginine methyl ester (\n<jats:sc>l<\/jats:sc>\u2010NAME) before induction of gastric ulceration by indomethacin. The gastroprotective effect of\u00a0\n<jats:sc>l<\/jats:sc>\u2010arginine was displayed only in adult rats with indomethacin\u2010induced gastric ulceration, as evidenced by a significant decrease in ulcer index, oxidative stress parameters, and mucosal myeloperoxidase activity along with increased mucosal PGE2 levels. Interestingly, the mucosal gene expressions of NF\u2010\u043aB, iNOS, and COX\u20102 were significantly suppressed by\u00a0\n<jats:sc>l<\/jats:sc>\u2010arginine pretreatment and aggregated upon pretreatment with\u00a0\n<jats:sc>l<\/jats:sc>\u2010NAME in both adult and aged rats treated with indomethacin. In conclusion,\u00a0\n<jats:sc>l<\/jats:sc>\u2010arginine protected the rats' gastric mucosa against indomethacin\u2010induced gastric ulceration, possibly, at least in part, by enhancement of mucosal nitric oxide\/PGE2 content along with suppressing gastric inflammation and oxidative stress. This study supposed that the gastroprotective effect of\u00a0\n<jats:sc>l<\/jats:sc>\u2010arginine depends on aging, and even so, the adoption of a new approach to gastric ulcer treatment for the aged population is warranted.<\/jats:p>","DOI":"10.1002\/jbt.23479","type":"journal-article","created":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T15:19:50Z","timestamp":1690125590000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Gastro\u2010protective effect of <scp>l<\/scp>\u2010arginine against nitric oxide deficiency\u2010related mucosal injury induced by indomethacin: Does age matter?"],"prefix":"10.1002","volume":"37","author":[{"given":"Gehan H.","family":"Heeba","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Minia University El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-9094","authenticated-orcid":false,"given":"Mohamed A.","family":"Morsy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy King Faisal University  Al\u2010Ahsa Saudi Arabia"},{"name":"Department of Pharmacology, Faculty of Medicine Minia University El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda E.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Agricultural Chemistry, Faculty of Agriculture Minia University  El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3770-7128","authenticated-orcid":false,"given":"Rania","family":"Abdel\u2010latif","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Minia University El\u2010Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,7,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000010665"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v19.i48.9439"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2009.04086.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2009.02.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1681.2001.03497.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.08.035"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22727-6"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-214-44087"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2006.04.013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2009.09.002"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2007.09.008"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013203217788"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/phrs.2001.0801"},{"key":"e_1_2_8_15_1","first-page":"681","volume":"10","author":"Al\u2010Rekabi B. 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