Time-dependent course of gastric ulcer healing and molecular markers profile modulated by increased gastric mucosal content of carbon monoxide released from its pharmacological donor

Evidence for Cytoprotective Effect of Carbon Monoxide Donor in the Development of Acute Esophagitis Leading to Acute Esophageal Epithelium Lesions

“…Chronic GERD may lead to the development of premalignant intestinal metaplasia called Barrett's esophagus with the presence of goblet cells, which are not normally observed within esophageal mucosa [1][2][3][4][36][37][38][39]. This phenomenon could be considered as a defensive esophageal adaptation to the altered physiological conditions [26][27][28][29][30][31][32][33][34][35][36][37][38][39]. However, even single and short-lasting exposure of esophageal structure to the low pH refluxate is known to induce local irritation, oxidation, and inflammation of esophageal mucosa, frequently resulting in necrotic erosions and desquamation of esophageal epithelium described as reflux esophagitis (RE) [27,40,41].…”

“…Expression for HMOX-1, HMOX-2, COX-1, COX-2, iNOS, nNOS, HIF-1α, annexin-A1, IL-1β, TNF-α, β-actin (ACTB) and succinate dehydrogenase complex (SDHA) was determined using specific primers [31][32][33]. Expression for IL-6R, IL-1R1, IL-1R2, IL-1RA, TNF-R2, NF-κB, c-Fos, c-Jun, SOCS3 was determined using specific primers described elsewhere [34].…”

“…Protein expression for Nrf-2, HMOX-1, HMOX-2, COX-1, COX-2, and TRPV1 in esophageal mucosa was determined using Western Blot, as described previously [32,33]. Rabbit monoclonal anti-HMOX-1 (ab68477, Abcam, Cambridge, UK) in dilution of 1:1000, rabbit polyclonal anti-COX-1 (13393-1-AP, Proteintech, Manchester, UK) in dilution of 1:1000, rabbit polyclonal anti-COX-2 (ab 15191, Abcam) in dilution of 1:1000, rabbit polyclonal anti-HMOX-2 (14817-1AP, Proteintech), rabbit polyclonal anti-Nrf-2 (16396-I-AP, Proteintech) in dilution of 1:500 and mouse monoclonal anti-GAPDH (60004-1-Ig, Proteintech) in dilution of 1:2000 were used as primary antibodies.…”

“…The intensity of bands was determined and analyzed using Image Studio 4.0 software (LI-COR). The expression of each protein of interest was determined using 5 samples per experimental group and obtained values were normalized to the expression of ACTB as loading control [32,33].…”

Gaseous Mediators as a Key Molecular Targets for the Development of Gastrointestinal-Safe Anti-Inflammatory Pharmacology

“…The range of CORMs reported so far is wide and comprises the most investigated ones [Mn2(CO)10] (CORM-1), tricarbonyldichlororuthenium (II) dimer [Ru(CO)3Cl2]2 (CORM-2) and tricarbonylchloro (glycinato)ruthenium (II) (CORM-3) ( Kautz et al, 2016 ). Numerous animal studies have confirmed that CO released from CORMs affords gastroprotection against gastric mucosal injury induced by ethanol, ischemia/reperfusion, stress or NSAIDs and has a beneficial influence by acceleration of gastric ulcers healing ( Magierowska et al, 2016 ; Takagi et al, 2016 ; Magierowski et al, 2017 ; Magierowska et al, 2018 ; Magierowska et al, 2019 ; Magierowska et al, 2019 ). What is more, Freitas et al (2006) have documented in their mice model of acute mesenteric inflammation evoked by carrageenan administration, that dimagnese decacarbonyl DMDC, a CO donor, remarkably decreased leukocyte adhesion and migration to the inflamed tissue and this effect was reversed by a soluble guanylate cyclase (sGC) inhibitor.…”