title: Aspirin renders the oesophageal mucosa more permeable to acid and pepsin.
abstract: OBJECTIVE
  To examine the effects of aspirin on the oesophageal mucosa and on acid- and pepsin-induced oesophagitis.
  
  
  METHODS
  The effects both of intraluminal (18 mg/ml) and of parenteral (100 mg/kg per h) aspirin on an in-vivo rabbit model of oesophagitis induced by acidified pepsin (pH 2) were studied. Oesophageal injury was assessed by macroscopic and microscopic scoring including the cell proliferation immunohistochemical parameter mib1. The mucosal barrier function was determined by hydrogen, potassium and haemoglobin flux rates.
  
  
  RESULTS
  Acidified saline alone caused no damage, but the addition of aspirin induced mucosal barrier damage (P < 0.05). The exposure of the oesophageal mucosa to acidified aspirin and then acidified pepsin significantly increased mucosal injury and mucosal barrier dysfunction compared with control experiments (exposure to acidified saline and acidified pepsin). This damage was significantly (P < 0.05) reduced (> 40%) by prostaglandin cotherapy (prostaglandin E2) administered before acidified aspirin exposure. Mucosal damage was less severe (P < 0.05) when the oesophageal mucosa was exposed to a pH 6 aspirin solution. Parenterally administered aspirin also increased the oesophageal damage induced by acidified pepsin compared with control experiments, but the damage was 23% lower than that obtained with intraluminal aspirin. Cell proliferation studies showed a significant increase in the number of positive cells in those experiments with a higher degree of damage and in those treated with prostaglandins.
  
  
  CONCLUSIONS
  Aspirin renders the oesophageal mucosa more permeable to acid and pepsin. These effects are in part pH-dependent and might be partially reversed by prostaglandin E2 cotherapy.
authors.affiliation: Service of Gastroenterology, Hospital Clínico, University of Zaragoza, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Lanas
authors.forename: F L
authors.initials: FL
authors.lastname: Sousa
authors.forename: J
authors.initials: J
authors.lastname: Ortego
authors.forename: F
authors.initials: F
authors.lastname: Esteva
authors.forename: J M
authors.initials: JM
authors.lastname: Blas
authors.forename: J
authors.initials: J
authors.lastname: Soria
authors.forename: R
authors.initials: R
authors.lastname: Sáinz
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004941:Esophagitis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006863:Hydrogen-Ion Concentration; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010434:Pepsin A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011817:Rabbits
chemical_list: D000143:Acids; D010434:Pepsin A; D015232:Dinoprostone; D001241:Aspirin