TY - JOUR
T1 - Gastro protective properties of the novel prostone SPI-8811 against acid-injured porcine mucosa
AU - Nighot, Meghali
AU - Moeser, Adam
AU - Ueno, Ryuji
AU - Blikslager, Anthony
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84867722871
UR - https://www.scopus.com/pages/publications/84867722871#tab=citedBy
U2 - 10.3748/wjg.v18.i34.4684
DO - 10.3748/wjg.v18.i34.4684
M3 - Article
C2 - 23002337
AN - SCOPUS:84867722871
SN - 1007-9327
VL - 18
SP - 4684
EP - 4692
JO - World journal of gastroenterology
JF - World journal of gastroenterology
IS - 34
ER -