Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa

Meghali Nighot, Adam Moeser, Ryuji Ueno, Anthony Blikslager

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

AIM: To evaluate the protective properties of novel prostone ClC-2 agonist SPI-8811 in porcine model of gastric acid injury. METHODS: Porcine gastric mucosa was mounted in Ussing chambers and injured by bathing mucosal tissues in an HCl Ringer's solution (pH = 1.5) with or without SP1-8811 (1 μmol/L), cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor (inhibitor 172, 10 μmol/L, apical) and ClC-2 inhibitor ZnCl2, 300 μmol/L, apical), on the apical surface of tissues. Transepithelial resistance and mucosal-to-serosal 3H-mannitol fluxes were measured over a 90-min period. Tissues were analyzed by morph metric techniques, Immunofluorescence and by western blots. RESULTS: Compared with control tissues, acid exposure decreased transepithelial electrical resistance (TER) and increased 3H-mannitol flux. Pretreatment of gastric mucosa with SPI-8811 was protective against acidinduced decreases in TER (TER, 50 Ω.cm2 vs 100 Ω.cm2) and abolished increases in flux (3H-mannitol flux, 0.10 μmol/L.cm2 vs 0.04 μmol/L.cm2). Evidence of histological damage in the presence of acid was markedly attenuated by SPI-0811. Immunofluorescence and western analysis for occludin revealed enhanced localization to the region of the tight junction (TJ) after treatment with SPI-8811. Pretreatment with the ClC-2 inhibitor ZnCl2, but not the selective CFTR inhibitor 172, attenuated SPI-8811-mediated mucosal protection, suggesting a role for ClC-2. Prostone may serve both protective and reparative roles in injured tissues. CONCLUSION: ClC-2 agonist SPI-8811 stimulated enhancement of mucosal barrier function by protecting TJ protein occludin in porcine gastric mucosa and thus protected the gastric acid injury in porcine stomach.

Original languageEnglish (US)
Pages (from-to)4684-4692
Number of pages9
JournalWorld journal of gastroenterology
Volume18
Issue number34
DOIs
StatePublished - 2012

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Fingerprint Dive into the research topics of 'Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa'. Together they form a unique fingerprint.

  • Cite this