{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T12:18:07Z","timestamp":1788092287628,"version":"build-2803163510"},"reference-count":59,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T00:00:00Z","timestamp":1620950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["N41\/DBS\/000106"],"award-info":[{"award-number":["N41\/DBS\/000106"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hydrogen sulfide (H2S) is an endogenously produced molecule with anti-inflammatory and cytoprotective properties. We aimed to investigate for the first time if a novel, esterase-sensitive H2S-prodrug, BW-HS-101 with the ability to release H2S in a controllable manner, prevents gastric mucosa against acetylsalicylic acid-induced gastropathy on microscopic and molecular levels. Wistar rats were pretreated intragastrically with vehicle, BW-HS-101 (0.5\u201350 \u03bcmol\/kg) or its analogue without the ability to release H2S, BW-iHS-101 prior to ASA administration (125 mg\/kg, intragastrically). BW-HS-101 was administered alone or in combination with nitroarginine (L-NNA, 20 mg\/kg, intraperitoneally) or zinc protoporphyrin IX (10 mg\/kg, intraperitoneally). Gastroprotective effects of BW-HS-101 were additionally evaluated against necrotic damage induced by intragastrical administration of 75% ethanol. Gastric mucosal damage was assessed microscopically, and gastric blood flow was determined by laser flowmetry. Gastric mucosal DNA oxidation and PGE2 concentration were assessed by ELISA. Serum and\/or gastric protein concentrations of IL-1\u03b1, IL-1\u03b2, IL-2, IL-4, IL-6, IL-10, IL-13, VEGF, GM-CSF, IFN-\u03b3, TNF-\u03b1, and EGF were determined by a microbeads\/fluorescent-based multiplex assay. Changes in gastric mucosal iNOS, HMOX-1, SOCS3, IL1-R1, IL1-R2, TNF-R2, COX-1, and COX-2 mRNA were assessed by real-time PCR. BW-HS-101 or BW-iHS-101 applied at a dose of 50 \u03bcmol\/kg protected gastric mucosa against ASA-induced gastric damage and prevented a decrease in the gastric blood flow level. H2S prodrug decreased DNA oxidation, systemic and gastric mucosal inflammation with accompanied upregulation of SOCS3, and EGF and HMOX-1 expression. Pharmacological inhibition of nitric oxide (NO) synthase but not carbon monoxide (CO)\/heme oxygenase (HMOX) activity by L-NNA or ZnPP, respectively, reversed the gastroprotective effect of BW-HS-101. BW-HS-101 also protected against ethanol-induced gastric injury formation. We conclude that BW-HS-101, due to its ability to release H2S in a controllable manner, prevents gastric mucosa against drugs-induced gastropathy, inflammation and DNA oxidation, and upregulate gastric microcirculation. Gastroprotective effects of this H2S prodrug involves endogenous NO but not CO activity and could be mediated by cytoprotective and anti-inflammatory SOCS3 and EGF pathways.<\/jats:p>","DOI":"10.3390\/ijms22105211","type":"journal-article","created":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T10:54:22Z","timestamp":1620989662000},"page":"5211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Novel Hydrogen Sulfide (H2S)-Releasing BW-HS-101 and Its Non-H2S Releasing Derivative in Modulation of Microscopic and Molecular Parameters of Gastric Mucosal Barrier"],"prefix":"10.3390","volume":"22","author":[{"given":"Dominik","family":"Bakalarz","sequence":"first","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"},{"name":"Department of Forensic Toxicology, Institute of Forensic Research, 31033 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-5389","authenticated-orcid":false,"given":"Edyta","family":"Korbut","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengnan","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingchen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3098-9617","authenticated-orcid":false,"given":"Dagmara","family":"W\u00f3jcik","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Danielak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4866-1102","authenticated-orcid":false,"given":"Katarzyna","family":"Magierowska","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4806-8042","authenticated-orcid":false,"given":"Slawomir","family":"Kwiecie\u0144","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-0065","authenticated-orcid":false,"given":"Tomasz","family":"Brzozowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4948-6617","authenticated-orcid":false,"given":"Monika","family":"Marcinkowska","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Jagiellonian University Medical College, 30688 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2200-5270","authenticated-orcid":false,"given":"Binghe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0175-5600","authenticated-orcid":false,"given":"Marcin","family":"Magierowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jagiellonian University Medical College, 31531 Cracow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.amjcard.2015.01.014","article-title":"Use of low-dose aspirin as secondary prevention of atherosclerotic cardiovascular disease in US adults (from the National Health Interview Survey, 2012)","volume":"115","author":"Fang","year":"2015","journal-title":"Am. 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