Gastroduodenal mucosal defence mechanisms and the action of non-steroidal anti-inflammatory agents.
This review summarises gastroduodenal protective mechanisms, the actions of non-steroidal anti-inflammatory (NSAI) agents on mucus and HCO3 secretions, and the basis of gastric mucosal injury induced by acetylsalicylic and salicylic acids (ASA and SA). Resistance to autodigestion by acid and pepsin present in gastric juice is multifactorial involving pre-epithelial (mucus-bicarbonate barrier) and post-epithelial (blood flow, acid-base balance) factors in addition to properties of the surface cell layer per se. The latter includes mucosal re-epithelialisation, a property which appears particularly important with respect to recovery from acute injury. A range of NSAI agents (ASA, fenclofenac, ibuprofen and indomethacin) inhibit gastric HCO3 transport in isolated mucosal preparations. Inhibition of duodenal HCO3 transport has been demonstrated in response to indomethacin in vitro and in vivo. These effects on secretion can be antagonised by exogenous prostaglandins of the E series. The layer of secreted mucus gel overlying the epithelial surface is not affected by NSAI drugs in the short term. However a number of these agents have been shown to inhibit glycoprotein biosynthesis by the epithelial cells. Thus loss of this protective coat could be anticipated during chronic drug exposure since erosion of adherent mucus by luminal shear and proteolysis would not be compensated by continued secretion. Detailed analysis of the gastric mucosal injury induced by salicylates both in vitro and in vivo reveals that much of the damage previously attributed to ASA is in fact due to the metabolic product SA. In this respect it is concluded that mucosal injury caused by ASA is due to a combination of two factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Garner
A
A
Allen
A
A
Rowe
P H
PH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin; D001639:Bicarbonates / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D012459:Salicylates; D020156:Salicylic Acid
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001639:Bicarbonates; D012459:Salicylates; D020156:Salicylic Acid; D001241:Aspirin