Katarzyna Magierowska1, Dominik Bakalarz2, Dagmara Wójcik1, Anna Chmura1, Magdalena Hubalewska-Mazgaj1, Sabina Licholai3, Edyta Korbut1, Slawomir Kwiecien1, Zbigniew Sliwowski1, Grzegorz Ginter1, Tomasz Brzozowski1, Marcin Magierowski4. 1. Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland. 2. Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland; Department of Forensic Toxicology, Institute of Forensic Research, 9 Westerplatte Street, 31-033 Cracow, Poland. 3. Department of Molecular Biology and Clinical Genetics, Jagiellonian University Medical College, 8 Skawinska Street, 31-066 Cracow, Poland. 4. Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland. Electronic address: m.magierowski@uj.edu.pl.
Abstract
BACKGROUND AND PURPOSE: Besides hydrogen sulfide (H2S) and nitric oxide (NO), carbon monoxide (CO) contributes to the maintenance of gastric mucosal integrity. We investigated increased CO bioavailability effects on time-dependent dynamics of gastric ulcer healing mediated by particular growth factors, anti-inflammatory and molecular pathways. EXPERIMENTAL APPROACH: Wistar rats with gastric ulcers induced by serosal acetic acid application (day 0) were treated i.g. throughout 3, 6 or 14 days with vehicle or CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2, 2.5 mg/kg). Gross and microscopic alterations in gastric ulcer size and gastric blood flow (GBF) at ulcer margin were determined by planimetry, histology and laser flowmetry, respectively. Gastric mRNA/protein expressions of platelet derived growth factors (PDGFA-D), insulin-like growth factor (IGF-1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGFA) and their receptors, heme oxygenases (HMOX), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX-2), hypoxia inducible factor (HIF)-1α, anti-inflammatory annexin-1 and transforming growth factor (TGF-β1) were assessed by real-time PCR or Western blot. TGF-β1-3 and IL-10 plasma concentration were measured using Luminex platform. Prostaglandin E2 content at ulcer margin was assessed by ELISA. KEY RESULTS: CORM-2 decreased ulcer area and increased GBF after 6 and 14 days of treatment comparing to vehicle. CO donor upregulated HGF, HGFr, VEGFR1, VEGFR2, TGF-β1, annexin-1 and maintained increased IGF-1, PDGFC and EGF expression at various time-intervals of ulcer healing. TGF-β3 and IL-10 plasma concentration were significantly increased after COMR-2 vs. vehicle. CONCLUSIONS: CO time-dependently accelerates gastric ulcer healing and raises GBF at ulcer margin by mechanism involving subsequent upregulation of anti-inflammatory, growth promoting and angiogenic factors response, not observed physiologically.
BACKGROUND AND PURPOSE: Besides hydrogen sulfide (H2S) and nitric oxide (NO), carbon monoxide (CO) contributes to the maintenance of gastric mucosal integrity. We investigated increased CO bioavailability effects on time-dependent dynamics of gastric ulcer healing mediated by particular growth factors, anti-inflammatory and molecular pathways. EXPERIMENTAL APPROACH: Wistar rats with gastric ulcers induced by serosal acetic acid application (day 0) were treated i.g. throughout 3, 6 or 14 days with vehicle or CO-releasing tricarbonyldichlororuthenium (II) dimer (CORM-2, 2.5 mg/kg). Gross and microscopic alterations in gastric ulcer size and gastric blood flow (GBF) at ulcer margin were determined by planimetry, histology and laser flowmetry, respectively. Gastric mRNA/protein expressions of platelet derived growth factors (PDGFA-D), insulin-like growth factor (IGF-1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGFA) and their receptors, heme oxygenases (HMOX), nuclear factor (erythroid-derived 2)-like 2 (Nrf-2), cyclooxygenase (COX-2), hypoxia inducible factor (HIF)-1α, anti-inflammatory annexin-1 and transforming growth factor (TGF-β1) were assessed by real-time PCR or Western blot. TGF-β1-3 and IL-10 plasma concentration were measured using Luminex platform. Prostaglandin E2 content at ulcer margin was assessed by ELISA. KEY RESULTS: CORM-2 decreased ulcer area and increased GBF after 6 and 14 days of treatment comparing to vehicle. COdonor upregulated HGF, HGFr, VEGFR1, VEGFR2, TGF-β1, annexin-1 and maintained increased IGF-1, PDGFC and EGF expression at various time-intervals of ulcer healing. TGF-β3 and IL-10 plasma concentration were significantly increased after COMR-2 vs. vehicle. CONCLUSIONS:CO time-dependently accelerates gastric ulcer healing and raises GBF at ulcer margin by mechanism involving subsequent upregulation of anti-inflammatory, growth promoting and angiogenic factors response, not observed physiologically.
Authors: Katarzyna Magierowska; Dominik Bakalarz; Dagmara Wójcik; Edyta Korbut; Aleksandra Danielak; Urszula Głowacka; Robert Pajdo; Grzegorz Buszewicz; Grzegorz Ginter; Marcin Surmiak; Sławomir Kwiecień; Anna Chmura; Marcin Magierowski; Tomasz Brzozowski Journal: Cells Date: 2020-05-12 Impact factor: 6.600
Authors: Dominik Bakalarz; Marcin Surmiak; Xiaoxiao Yang; Dagmara Wójcik; Edyta Korbut; Zbigniew Śliwowski; Grzegorz Ginter; Grzegorz Buszewicz; Tomasz Brzozowski; Jakub Cieszkowski; Urszula Głowacka; Katarzyna Magierowska; Zhixiang Pan; Binghe Wang; Marcin Magierowski Journal: Acta Pharm Sin B Date: 2020-08-24 Impact factor: 11.413