title: Nitric oxide, afferent sensory nerves, and antioxidative enzymes in the mechanism of protection mediated by tricarbonyldichlororuthenium(II) dimer and sodium hydrosulfide against aspirin-induced gastric damage.
abstract: Aspirin exerts side effects within the gastrointestinal tract. Hydrogen sulfide (H2S) and carbon monoxide (CO) have been implicated in gastroprotection but the mechanism of beneficial action of these gaseous mediators against aspirin-induced damage has not been fully studied. We determined the involvement of afferent sensory neurons, calcitonin-gene-related peptide (CGRP), lipid peroxidation, and nitric oxide (NO) biosynthesis in gastroprotection of H2S-releasing NaHS and CO-releasing tricarbonyldichlororuthenium(II) dimer (CORM-2) against aspirin-induced injury.
  
  
  
  Wistar rats with or without capsaicin-induced denervation of sensory neurons were pretreated with vehicle, CORM-2 (5 mg/kg intragastrically), or NaHS (5 mg/kg intragastrically) with or without capsazepine (5 mg/kg intragastrically) or NG-nitro-L-arginine (L-NNA, 20 mg/kg intraperitoneally). The areas of aspirin-induced lesions and gastric blood flow (GBF) were assessed by planimetry and laser flowmetry respectively. Gastric mucosal messenger RNA and/or protein expression of CGRP, heme oxygenase 1, inducible nitric oxide synthase, cyclooxygenase 2, interleukin-1β, glutathione peroxidase 1 (GPx-1), and superoxide dismutase was determined by real-time PCR or Western blot. Malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) content was determined by colorimetric assay.
  
  
  
  Aspirin caused gastric lesions, decreased GBF, and raised MDA content, but pretreatment with NaHS and CORM-2 reduced these effects. Capsaicin-induced denervation or co-treatment with capsazepine reversed the gastroprotective and vasodilatory effects of NaHS but not those of CORM-2. L-NNA reversed NaHS-induced gastroprotection and partly reduced CORM-2-induced gastroprotection. NaHS and CORM-2 decreased MDA and 4-HNE content, restoring GPx-1 protein expression.
  
  
  
  We conclude that H2S- but not CO-mediated gastroprotection against aspirin-induced injury involves afferent sensory nerves and partly NO activity. NaHS and CORM-2 prevented aspirin-induced gastric mucosal lipid peroxidation via restoration of microcirculation and antioxidative GPx-1 protein expression.
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland. m.magierowski@uj.edu.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Magierowski
authors.affiliation: Department of Genetic Research and Nutrigenomics, Malopolska Centre of Biotechnology, Jagiellonian University, 7A Gronostajowa Street, 30-387, Cracow, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hubalewska-Mazgaj
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Magierowska
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Wojcik
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Sliwowski
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Kwiecien
authors.affiliation: Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531, Cracow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brzozowski
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism; D001241:Aspirin / Q000633:toxicity*; D015153:Blotting, Western; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002248:Carbon Monoxide / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D005979:Glutathione Peroxidase / Q000235:genetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000378:metabolism; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013440:Sulfides / Q000494:pharmacology*; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D009942:Organometallic Compounds; D013440:Sulfides; C447082:tricarbonyldichlororuthenium (II) dimer; D009569:Nitric Oxide; D002248:Carbon Monoxide; D005979:Glutathione Peroxidase; C025451:sodium bisulfide; D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D001241:Aspirin; D002211:Capsaicin; D000094765:Glutathione Peroxidase GPX1; C000722069:Gpx1 protein, rat
keywords: Afferent sensory nerves; Aspirin; Carbon monoxide; Hydrogen sulfide; Nitric oxide