{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T09:17:40Z","timestamp":1773307060820,"version":"3.50.1"},"reference-count":65,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2017,8,30]],"date-time":"2017-08-30T00:00:00Z","timestamp":1504051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Science and Higher Education and Jagiellonian University Medical College","award":["K\/DSC\/003587"],"award-info":[{"award-number":["K\/DSC\/003587"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Carbon monoxide (CO), a gaseous mediator produced by haem oxygenases (HOs), has been shown to prevent stress\u2010, ethanol\u2010, aspirin\u2010 and alendronate\u2010induced gastric damage; however, its role in gastric ulcer healing has not been fully elucidated. We investigated whether CO released from tricarbonyldichlororuthenium (II) dimer (CORM\u20102) can affect gastric ulcer healing and determined the mechanisms involved in this healing action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Gastric ulcers were induced in Wistar rats by serosal application of acetic acid. Animals received 9\u00a0days of treatment with RuCl<jats:sub>3<\/jats:sub>[2.5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>intragastrically (i.g.)], haemin (5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>i.g.), CORM\u20102 (0.1\u201310\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>i.g.) administered alone or with zinc protoporphyrin IX (ZnPP, 10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>i.g.), 1H\u2010[1,2,4]oxadiazolo[4,3\u2010a]quinoxalin\u20101\u2010one (ODQ, 5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>i.g.), N<jats:sup>G<\/jats:sup>\u2010nitro\u2010<jats:sc>l<\/jats:sc>\u2010arginine (<jats:sc>l<\/jats:sc>\u2010NNA, 15\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>i.g.), indomethacin (5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>i.g.) or glibenclamide (10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>i.g.). Gastric ulcer area and gastric blood flow (GBF) were assessed planimetrically, microscopically and by laser flowmeter respectively. Gastric mRNA\/protein expressions of EGF, EGF receptors, VEGFA, HOs, nuclear factor (erythroid\u2010derived 2)\u2010like 2 (Nrf2), COX\u20102, hypoxia\u2010inducible factor (HIF)\u20101\u03b1 and pro\u2010inflammatory iNOS, IL\u20101\u03b2 and TNF\u2010\u03b1 were determined by real\u2010time PCR or Western blots.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>CORM\u20102 and haemin but not RuCl<jats:sub>3<\/jats:sub>or ZnPP decreased ulcer size while increasing GBF. These effects were reduced by ODQ, indomethacin,<jats:sc>l<\/jats:sc>\u2010NNA and glibenclamide. CORM\u20102 significantly decreased the expression of pro\u2010inflammatory markers, Nrf2\/HO1 and HIF\u20101\u03b1, and up\u2010regulated EGF.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>CO released from CORM\u20102 or endogenously produced by the HO1\/Nrf2 pathway accelerates gastric ulcer healing<jats:italic>via<\/jats:italic>an increase in GBF, an up\u2010regulation in EGF expression and down\u2010regulation of the inflammatory response.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13968","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T16:42:42Z","timestamp":1501692162000},"page":"3654-3668","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Carbon monoxide released from its pharmacological donor, tricarbonyldichlororuthenium (II) dimer, accelerates the healing of pre\u2010existing gastric ulcers"],"prefix":"10.1111","volume":"174","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0175-5600","authenticated-orcid":false,"given":"Marcin","family":"Magierowski","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Magierowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Hubalewska\u2010Mazgaj","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zbigniew","family":"Sliwowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grzegorz","family":"Ginter","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Pajdo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Chmura","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Slawomir","family":"Kwiecien","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Brzozowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Jagiellonian University Medical College Cracow Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,8,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13353"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.296"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053319"},{"key":"e_1_2_11_6_1","first-page":"501","article-title":"The adaptive role of nitric oxide and hydrogen sulphide in vasoactive responses of thoracic aorta is triggered already in young spontaneously hypertensive rats","volume":"67","author":"Cacanyiova S","year":"2016","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ANE.0000132695.77191.F3"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcma.2013.02.001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/762514"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90634-3"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2007.09.095"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.04.041"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201400347"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.5772\/17640"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.077917"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2014.11.034"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.05.023"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(96)68040-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v9.i8.1767"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02063260"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22287"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4944"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/372746a0"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.47.6.762"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.5604\/17322693.1087527"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2010.00872.x"},{"key":"e_1_2_11_28_1","first-page":"717","article-title":"Role of sensory afferent nerves, lipid peroxidation and antioxidative enzymes in the carbon monoxide\u2010induced gastroprotection against stress ulcerogenesis","volume":"67","author":"Kwiecien S","year":"2016","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_11_29_1","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/4690857","article-title":"S\u2010Propargyl\u2010cysteine exerts a novel protective effect on methionine and choline deficient diet\u2010induced fatty liver via Akt\/Nrf2\/HO\u20101 pathway","author":"Li W","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140493"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17040442"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-017-1323-4"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms15034946"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.11.001"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22020295"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20059099"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-016-4280-5"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.2.10.3290025"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42488-4"},{"key":"e_1_2_11_40_1","first-page":"409","article-title":"Cyclooxygenase\u20102 (COX\u20102) is the key event in pathophysiology of Barrett's esophagus: lesson from experimental animal model and human subjects","volume":"61","author":"Majka J","year":"2010","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12955"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.1104"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh0202.104530"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.060745"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.1321"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02235252"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/74680"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.02.008"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.01.012"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2005"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.20005"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_2_11_53_1","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/S0022-3565(24)37734-1","article-title":"Role of cyclooxygenase\u20102 in the healing of gastric ulcers in rats","volume":"286","author":"Shigeta J","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.3.1894"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2014.05.002"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_11_57_1","first-page":"625","article-title":"Experimental healing of preexisting gastric ulcers induced by hormones controlling food intake ghrelin, orexin\u2010A and nesfatin\u20101 is impaired under diabetic conditions. A key to understanding the diabetic gastropathy?","volume":"64","author":"Szlachcic A","year":"2013","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2016.1189546"},{"issue":"5","key":"e_1_2_11_59_1","first-page":"G1137","article-title":"Localization of cyclooxygenase\u20102 and regulation of its mRNA expression in gastric ulcers in rats","volume":"275","author":"Takahashi S","year":"1998","journal-title":"Am J Physiol"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.175216"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712803413962"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-005-2803-6"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp100199m"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.2.286"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/343082a0"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.06.029"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13968","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13968","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T20:07:19Z","timestamp":1750795639000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.13968"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,30]]},"references-count":65,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1111\/bph.13968"],"URL":"https:\/\/doi.org\/10.1111\/bph.13968","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,30]]},"assertion":[{"value":"2017-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-07-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}