Prevention by mild irritants of gastric necrosis produced in rats by sodium taurocholate.

Acidified sodium taurocholate, 80 mmol given orally to rats, produced extensive gastric lesions within 1 hr. A variety of milk irritants (0.15--0.35 N HCl; 10--25% ethanol; 5 mmol of acidified taurocholate) given orally 15 min before 80 mmol of taurocholate protected the stomach in a dose-dependent manner. This phenomenon is called "adaptive cytoprotection." The mild irritants are believed to elicit the endogenous formation of prostaglandin (PG) by the gastric mucosa; these PGs would prevent gastric injury through their cytoprotective property. Results with indomethacin, an inhibitor of the enzyme (PG cyclooxygenase) that transforms arachidonic acid into PG, supports this conclusion. Indomethacin given subcutaneously or orally 75 min before the mild irritants blocked their protective effect, presumably by preventing the formation of PG by the stomach. Endogenous PG may be formed continually by the stomach in response to the various "irritants" normally present in the lumen, such as foodstuffs at a wide range of pH and temperatures, exogenous agents such as alcohol and drugs, as well as bile refluxing from the duodenum. This biosynthesis of PG may be a physiological phenomenon that explains why the stomach remains intact in spite of being bathed with noxious agents.