{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:22:20Z","timestamp":1780917740473,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T00:00:00Z","timestamp":1487116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["UMO-2015\/16\/T\/NZ4\/00176"],"award-info":[{"award-number":["UMO-2015\/16\/T\/NZ4\/00176"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Statutory grant from Jagiellonian University Medical College in Cracow, Poland","award":["K\/ZDS\/004600"],"award-info":[{"award-number":["K\/ZDS\/004600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Hydrogen sulfide (H2S) is an endogenous mediator, synthesized from l-cysteine by cystathionine \u03b3-lyase (CSE), cystathionine \u03b2-synthase (CBS) or 3-mercaptopyruvate sulfurtransferase (3-MST). The mechanism(s) involved in H2S-gastroprotection against ischemia\/reperfusion (I\/R) lesions and their time-dependent progression into deeper gastric ulcerations have been little studied. We determined the effect of l-cysteine, H2S-releasing NaHS or slow H2S releasing compound GYY4137 on gastric blood flow (GBF) and gastric lesions induced by 30 min of I followed by 3, 6, 24 and 48 h of R. Role of endogenous prostaglandins (PGs), afferent sensory nerves releasing calcitonin gene-related peptide (CGRP), the gastric expression of hypoxia inducible factor (HIF)-1\u03b1 and anti-oxidative enzymes were examined. Rats with or without capsaicin deactivation of sensory nerves were pretreated i.g. with vehicle, NaHS (18\u2013180 \u03bcmol\/kg) GYY4137 (90 \u03bcmol\/kg) or l-cysteine (0.8\u201380 \u03bcmol\/kg) alone or in combination with (1) indomethacin (14 \u03bcmol\/kg i.p.), SC-560 (14 \u03bcmol\/kg), celecoxib (26 \u03bcmol\/kg); (2) capsazepine (13 \u03bcmol\/kg i.p.); and (3) CGRP (2.5 nmol\/kg i.p.). The area of I\/R-induced gastric lesions and GBF were measured by planimetry and H2-gas clearance, respectively. Expression of mRNA for CSE, CBS, 3-MST, HIF-1\u03b1, glutathione peroxidase (GPx)-1, superoxide dismutase (SOD)-2 and sulfide production in gastric mucosa compromised by I\/R were determined by real-time PCR and methylene blue method, respectively. NaHS and l-cysteine dose-dependently attenuated I\/R-induced lesions while increasing the GBF, similarly to GYY4137 (90 \u03bcmol\/kg). Capsaicin denervation and capsazepine but not COX-1 and COX-2 inhibitors reduced NaHS- and l-cysteine-induced protection and hyperemia. NaHS increased mRNA expression for SOD-2 and GPx-1 but not that for HIF-1\u03b1. NaHS which increased gastric mucosal sulfide release, prevented further progression of acute I\/R injury into deeper gastric ulcers at 6, 24 and 48 h of R. We conclude that H2S-induced gastroprotection against I\/R-injury is due to increase in gastric microcirculation, anti-oxidative properties and afferent sensory nerves activity but independent on endogenous prostaglandins.<\/jats:p>","DOI":"10.3390\/molecules22020295","type":"journal-article","created":{"date-parts":[[2017,2,15]],"date-time":"2017-02-15T10:09:07Z","timestamp":1487153347000},"page":"295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Exogenous and Endogenous Hydrogen Sulfide Protects Gastric Mucosa against the Formation and Time-Dependent Development of Ischemia\/Reperfusion-Induced Acute Lesions Progressing into Deeper Ulcerations"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0175-5600","authenticated-orcid":false,"given":"Marcin","family":"Magierowski","sequence":"first","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Magierowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Hubalewska-Mazgaj","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"},{"name":"Department of Genetic Research and Nutrigenomics, Malopolska Centre of Biotechnology, Jagiellonian University, 30-387 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Sliwowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pajdo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Ginter","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Slawomir","family":"Kwiecien","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Brzozowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31-531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1089\/ars.2011.4351","article-title":"Hydrogen sulfide: An endogenous mediator of resolution of inflammation and injury","volume":"17","author":"Wallace","year":"2012","journal-title":"Antioxid. Redox Signal"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1089\/ars.2009.2657","article-title":"Interactions of multiple gas-transducing systems: Hallmarks and uncertainties of CO, NO, and H2S gas biology","volume":"13","author":"Kajimura","year":"2010","journal-title":"Antioxid. Redox Signal"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1089\/152308603768295249","article-title":"The gasotransmitter role of hydrogen sulfide","volume":"5","author":"Wang","year":"2003","journal-title":"Antioxid. Redox Signal"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1096\/fj.02-0211hyp","article-title":"Two\u2019s company, three\u2019s a crowd: can H2S be the third endogenous gaseous transmitter?","volume":"16","author":"Wang","year":"2002","journal-title":"FASEB J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.5604\/17322693.1087527","article-title":"Carbon monoxide in human physiology\u2014Its role in the gastrointestinal tract","volume":"68","author":"Jasnos","year":"2014","journal-title":"Postepy Hig. Med. Dosw."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9099","DOI":"10.3390\/molecules20059099","article-title":"Gaseous mediators nitric oxide and hydrogen sulfide in the mechanism of gastrointestinal integrity, protection and ulcer healing","volume":"20","author":"Magierowski","year":"2015","journal-title":"Molecules"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2118","DOI":"10.1096\/fj.06-6270fje","article-title":"Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation","volume":"20","author":"Zanardo","year":"2006","journal-title":"FASEB J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1042\/bj2060267","article-title":"Characterization of the enzymatic capacity for cysteine desulphydration in liver and kidney of the rat","volume":"206","author":"Stipanuk","year":"1982","journal-title":"Biochem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11455","DOI":"10.1016\/S0021-9258(19)49931-6","article-title":"Rat cystathionine beta-synthase. Gene organization and alternative splicing","volume":"267","author":"Swaroop","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1093\/jb\/mvp111","article-title":"Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and produces hydrogen sulfide","volume":"146","author":"Shibuya","year":"2009","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.5604\/17322693.1038356","article-title":"Role of hydrogen sulfide in the physiology of gastrointestinal tract and in the mechanism of gastroprotection","volume":"67","author":"Magierowski","year":"2013","journal-title":"Postepy Hig. Med. Dosw."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1248\/bpb.34.789","article-title":"Regulation of colonic ion transport by gasotransmitters","volume":"34","author":"Pouokam","year":"2011","journal-title":"Biol. Pharm. Bull."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1748-1716.2010.02152.x","article-title":"Stimulation of duodenal HCO3\u2212 secretion by hydrogen sulfide in rats: Relation to prostaglandins, nitric oxide and sensory neurons","volume":"201","author":"Ise","year":"2011","journal-title":"Acta Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1042\/CBI20090368","article-title":"Hydrogen sulfide induces human colon cancer cell proliferation: role of Akt, ERK and p21","volume":"34","author":"Cai","year":"2010","journal-title":"Cell Biol. Int."},{"key":"ref_15","first-page":"553","article-title":"Diallyl disulfide inhibits the proliferation of HT-29 human colon cancer cells by inducing differentially expressed genes","volume":"4","author":"Huang","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/j.1440-1681.2007.04812.x","article-title":"Hydrogen sulfide-induced hypothermia attenuates stress-related ulceration in rats","volume":"35","author":"Lou","year":"2008","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4070","DOI":"10.1096\/fj.07-8669com","article-title":"Hydrogen sulfide enhances ulcer healing in rats","volume":"21","author":"Wallace","year":"2007","journal-title":"FASEB J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3176","DOI":"10.1007\/s10620-016-4280-5","article-title":"Hydrogen sulfide and carbon monoxide protect gastric mucosa compromised by mild stress against alendronate injury","volume":"61","author":"Magierowski","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.phrs.2016.11.001","article-title":"Interaction between endogenous carbon monoxide and hydrogen sulfide in the mechanism of gastroprotection against acute aspirin-induced gastric damage","volume":"114","author":"Magierowski","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ejphar.2014.01.009","article-title":"Hydrogen sulfide protected gastric epithelial cell from ischemia\/reperfusion injury by Keap1 s-sulfhydration, MAPK dependent anti-apoptosis and NF-\u03baB dependent anti-inflammation pathway","volume":"725","author":"Guo","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3892\/etm.2012.870","article-title":"Protective effect of endogenous hydrogen sulfide against oxidative stress in gastric ischemia-reperfusion injury","volume":"5","author":"Cui","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1007\/s10620-012-2051-5","article-title":"Gastroprotective effect of NaHS against mucosal lesions induced by ischemia-reperfusion injury in rat","volume":"57","author":"Mard","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1161\/CIRCULATIONAHA.107.753467","article-title":"Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide","volume":"117","author":"Li","year":"2008","journal-title":"Circulation"},{"key":"ref_24","first-page":"G48","article-title":"Polymorphonuclear leukocyte infiltration into gastric mucosa after ischemia\u2013reperfusion","volume":"266","author":"Andrews","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_25","first-page":"G263","article-title":"Gastric epithelial damage induced by local ischemia\u2013reperfusion with or without exogenous acid","volume":"266","author":"Kawai","year":"1994","journal-title":"Am. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/978-1-4615-3404-4_27","article-title":"Ischemia\u2013reperfusion injury and free radical involvement in gastric mucosal disorders","volume":"316","author":"Yoshikawa","year":"1992","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1007\/BF02088232","article-title":"Gastric injury induced by ethanol and ischemia\u2013reperfusion in the rat. Differing roles for lipid peroxidation and oxygen radicals","volume":"41","author":"Smith","year":"1996","journal-title":"Dig. Dis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/S0014-2999(00)00287-9","article-title":"Role of gastric acid secretion in progression of acute gastric erosions induced by ischemia reperfusion into gastric ulcers","volume":"398","author":"Brzozowski","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Magierowski, M., Jasnos, K., Kwiecien, S., Drozdowicz, D., Surmiak, M., Strzalka, M., Ptak-Belowska, A., Wallace, J.L., and Brzozowski, T. (2015). Endogenous prostaglandins and afferent sensory nerves in gastroprotective effect of hydrogen sulfide against stress-induced gastric lesions. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118972"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1111\/j.1432-2277.2012.01514.x","article-title":"Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia\/reperfusion injury","volume":"25","author":"Bos","year":"2012","journal-title":"Transpl. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.3892\/etm.2012.733","article-title":"Endogenous hydrogen sulfide mediates the cardioprotection induced by ischemic postconditioning in the early reperfusion phase","volume":"4","author":"Huang","year":"2012","journal-title":"Exp. Ther. Med."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Snijder, P.M., de Boer, R.A., Bos, E.M., van den Born, J.C., Ruifrok, W.P., Vreeswijk-Baudoin, I., van Dijk, M.C., Hillebrands, J.L., Leuvenink, H.G., and van Goor, H. (2013). Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063291"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"203","DOI":"10.7555\/JBR.28.20140037","article-title":"GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats","volume":"29","author":"Meng","year":"2015","journal-title":"J. Biomed. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1681\/ASN.2012030268","article-title":"Cystathionine \u03b3-lyase protects against renal ischemia\/reperfusion by modulating oxidative stress","volume":"24","author":"Bos","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1053\/j.gastro.2009.04.012","article-title":"Endogenous and exogenous hydrogen sulfide promotes resolution of colitis in rats","volume":"137","author":"Wallace","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ejphar.2006.02.032","article-title":"Ghrelin-induced gastroprotection against ischemia-reperfusion injury involves an activation of sensory afferent nerves and hyperemia mediated by nitric oxide","volume":"536","author":"Konturek","year":"2006","journal-title":"Eur. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.3748\/wjg.v17.i14.1915","article-title":"Oxidative stress and hypoxia-induced factor 1\u03b1 expression in gastric ischemia","volume":"17","author":"Wang","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"ref_38","first-page":"133","article-title":"Role of afferent nerves and sensory peptides in the mediation of hepatic artery buffer response","volume":"56","author":"Biernat","year":"2005","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_39","first-page":"41","article-title":"Ghrelin ameliorates colonic inflammation. Role of nitric oxide and sensory nerves","volume":"60","author":"Konturek","year":"2009","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1111\/bph.12562","article-title":"H2S modulates duodenal motility in male rats via activating TRPV1 and K(ATP) channels","volume":"171","author":"Lu","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0024-3205(96)00500-0","article-title":"A new gastric ulcer model induced by ischemia-reperfusion in the rat: Role of leukocytes on ulceration in rat stomach","volume":"59","author":"Wada","year":"1996","journal-title":"Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4946","DOI":"10.3390\/ijms15034946","article-title":"Exogenous Asymmetric Dimethylarginine (ADMA) in Pathogenesis of Ischemia-Reperfusion-Induced Gastric Lesions: Interaction with Protective Nitric Oxide (NO) and Calcitonin Gene-Related Peptide (CGRP)","volume":"15","author":"Magierowski","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_43","first-page":"261","article-title":"Role of curcumin in protection of gastric mucosa against stress-induced gastric mucosal damage. Involvement of hypoacidity, vasoactive mediators and sensory neuropeptides","volume":"67","author":"Czekaj","year":"2016","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_44","first-page":"717","article-title":"Role of sensory afferent nerves, lipid peroxidation and antioxidative enzymes in the carbon monoxide-induced gastroprotection against stress ulcerogenesis","volume":"67","author":"Kwiecien","year":"2016","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0014-2999(94)00674-V","article-title":"Exogenous and endogenous cholecystokinin protects gastric mucosa against the damage caused by ethanol in rats","volume":"273","author":"Konturek","year":"1995","journal-title":"Eur. J. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Magierowska, K., Magierowski, M., Hubalewska-Mazgaj, M., Adamski, J., Surmiak, M., Sliwowski, Z., Kwiecien, S., and Brzozowski, T. (2015). Carbon monoxide (CO) released from tricarbonyldichlororuthenium(II) dimer (CORM-2) in gastroprotection against experimental ethanol\u2013induced gastric damage. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140493"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Magierowska, K., Magierowski, M., Surmiak, M., Adamski, J., Mazur-Bialy, A.I., Pajdo, R., Sliwowski, Z., Kwiecien, S., and Brzozowski, T. (2016). Protective role of carbon monoxide (CO) produced by heme oxygenase and derived from CO\u2013releasing molecule CORM-2 in pathogenesis of stress\u2013induced gastric lesions. Lack of involvement of nitric oxide (NO). Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17040442"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/2\/295\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:28:20Z","timestamp":1760207300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/2\/295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,15]]},"references-count":48,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,2]]}},"alternative-id":["molecules22020295"],"URL":"https:\/\/doi.org\/10.3390\/molecules22020295","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,15]]}}}