The role of an alginate suspension on pepsin and bile acids - key aggressors in the gastric refluxate. Does this have implications for the treatment of gastro-oesophageal reflux disease?
OBJECTIVE
During a reflux event the oesophagus is exposed to a heterogeneous mixture of gastric juice components. The role of non-acid components of the refluxate in causing damage to the oesophagus is now well established but no therapeutic option exists to address this.


METHODS
The role of Gaviscon Advance (GA), a raft-forming alginate suspension, in protecting the oesophagus from damage by pepsin and bile acids (aggressors) was investigated using a series of in-vitro models.


RESULTS
GA was able to dose-dependently inhibit pepsin activity over and above the neutralisation effect of the formulation. This was evident against both protein and collagen substrates using two distinct colorimetric assays. GA was able to retard the diffusion of pepsin and multiple bile acids using a Franz cell model. Using the raft-forming mode of action GA was able to remove both pepsin and multiple bile acids from a simulated reflux event. There was capacity in the GA raft to accommodate aggressors from multiple reflux events.


CONCLUSIONS
GA can specifically remove both pepsin and bile acids from the refluxate, limit their diffusion and affect enzymatic activity of pepsin. There is a role for GA to reduce the damaging potential of the refluxate and thus protect the oesophagus.
Strugala
Vicki
V
Technostics Ltd, Hull, UK. vicki.strugala@technostics.com
Avis
Jeanine
J
Jolliffe
Ian G
IG
Johnstone
Lesley M
LM
Dettmar
Peter W
PW
D000464:Alginates / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001639:Bicarbonates / Q000008:administration & dosage / Q000494:pharmacology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D003124:Colorimetry / Q000379:methods; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004947:Esophagus / Q000187:drug effects / Q000473:pathology; D005764:Gastroesophageal Reflux / Q000188:drug therapy / Q000378:metabolism; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D010434:Pepsin A / Q000187:drug effects / Q000378:metabolism*; D017680:Potassium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine
D000464:Alginates; D001639:Bicarbonates; D001647:Bile Acids and Salts; D004338:Drug Combinations; D006603:Hexuronic Acids; D017680:Potassium Compounds; D020723:Glucuronic Acid; D010434:Pepsin A; C026329:potassium bicarbonate