TY - JOUR
T1 - Mucosal protection by sucralfate and its components in acid-exposed rabbit esophagus
AU - Orlando, Roy C.
AU - Turjman, Nabila A.
AU - Tobey, Nelia A.
AU - Schreiner, Virginia J.
AU - Powell, Don W.
N1 - Funding Information:
Received August 14,1 986.A ccepted March 2, 1987. Address requests for reprints to: Roy C. Orlando, M.D., Division of Digestive Diseases and Nutrition, 324 Clinical Sciences Building 229H, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514. This research was funded in part by a grant from Marion Laboratories and by National Institutes of Health grant l-ROl-DK36013-OlAl. The authors thank Sandra F. Woody for expert technical assistance in the preparation of the manuscript. 0 1987 by the American Gastroenterological Association 0016-50851871S3.50
PY - 1987/8
Y1 - 1987/8
N2 - Sucralfate has been reported to protect the esophageal epithelium of the rabbit and cat against acid injury. To determine the contribution of its components, aluminum hydroxide and sucrose octasulfate (SOS), rabbit esophageal epithelia were mounted in Ussing chambers to monitor changes in electrical resistance (R) upon exposure to HCl (pH 1.4-1.6). In untreated tissues, acidification of the luminal bath produced a progressive decline in R, indicating increased epithelial permeability. Sucralfate added to the luminal bath 45 min after acidification increased R to preexposure levels-an effect accompanied by increased luminal pH. Similar to sucralfate, aluminum hydroxide added to the acidified bath increased R and luminal pH. However, the effect of aluminum hydroxide could be abolished by titration with HCl to maintain pH similar to acid-treated control tissues. Tissues treated with sucralfate and whose luminal solutions were titrated with HCl to maintain pH similar to controls no longer exhibited an increase in R but, in contrast to aluminum hydroxide treatment, the acid-induced decline in R was prevented. This action of sucralfate was shown to be a property of its other component, SOS. Sucrose octasulfate, like acid-titrated sucralfate solutions, did not increase luminal bath pH, yet prevented the acid-induced decline in R. Confirmation of protection by SOS was shown by additional morphologic and flux studies. Thus 1 h after luminal bath acidification in the Ussing chamber, SOS-treated tissues demonstrated less damage (injury score 0.6 ± 0.4 vs. 1.6 ± 0.3, p < 0.05) and lower permeability to mannitol (0.003 ± 0.001 vs. 0.013 ± 0.005 μmol/h · cm2, p < 0.05) than untreated tissues. Similarly, 1 h of luminal perfusion with HCl in vivo produced less damage (injury score 1.3 ± 0.5 vs. 3.5 ± 0.4, p < 0.05) and less H+ efflux from the lumen in SOS-treated than untreated tissues. These results indicate that sucralfate can protect against acid injury in esophagus and that this protection is mediated by (a) intraluminal pH buffering through its content of aluminum hydroxide and (b) enhancing mucosal defense against H+ entry and injury through its content of SOS.
AB - Sucralfate has been reported to protect the esophageal epithelium of the rabbit and cat against acid injury. To determine the contribution of its components, aluminum hydroxide and sucrose octasulfate (SOS), rabbit esophageal epithelia were mounted in Ussing chambers to monitor changes in electrical resistance (R) upon exposure to HCl (pH 1.4-1.6). In untreated tissues, acidification of the luminal bath produced a progressive decline in R, indicating increased epithelial permeability. Sucralfate added to the luminal bath 45 min after acidification increased R to preexposure levels-an effect accompanied by increased luminal pH. Similar to sucralfate, aluminum hydroxide added to the acidified bath increased R and luminal pH. However, the effect of aluminum hydroxide could be abolished by titration with HCl to maintain pH similar to acid-treated control tissues. Tissues treated with sucralfate and whose luminal solutions were titrated with HCl to maintain pH similar to controls no longer exhibited an increase in R but, in contrast to aluminum hydroxide treatment, the acid-induced decline in R was prevented. This action of sucralfate was shown to be a property of its other component, SOS. Sucrose octasulfate, like acid-titrated sucralfate solutions, did not increase luminal bath pH, yet prevented the acid-induced decline in R. Confirmation of protection by SOS was shown by additional morphologic and flux studies. Thus 1 h after luminal bath acidification in the Ussing chamber, SOS-treated tissues demonstrated less damage (injury score 0.6 ± 0.4 vs. 1.6 ± 0.3, p < 0.05) and lower permeability to mannitol (0.003 ± 0.001 vs. 0.013 ± 0.005 μmol/h · cm2, p < 0.05) than untreated tissues. Similarly, 1 h of luminal perfusion with HCl in vivo produced less damage (injury score 1.3 ± 0.5 vs. 3.5 ± 0.4, p < 0.05) and less H+ efflux from the lumen in SOS-treated than untreated tissues. These results indicate that sucralfate can protect against acid injury in esophagus and that this protection is mediated by (a) intraluminal pH buffering through its content of aluminum hydroxide and (b) enhancing mucosal defense against H+ entry and injury through its content of SOS.
UR - http://www.scopus.com/inward/record.url?scp=0023194983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0023194983&partnerID=8YFLogxK
U2 - 10.1016/0016-5085(87)91026-2
DO - 10.1016/0016-5085(87)91026-2
M3 - Article
C2 - 3596173
AN - SCOPUS:0023194983
SN - 0016-5085
VL - 93
SP - 352
EP - 361
JO - Gastroenterology
JF - Gastroenterology
IS - 2
ER -