Arachidonic acid is a polyunsaturated fatty acid precursor to prostaglandin formation in the stomach. When applied topically to gastric mucosa it prevents injury from a variety of damaging agents, similar to the effects observed with exogenous prostaglandins. Alternatively, fatty acids could act as mild irritants and protect the gastric mucosa in an adaptive cytoprotective process. This study was undertaken to ascertain whether arachidonic acid attenuates gastric injury from bile acid by acting as a mild irritant to the gastric epithelium or by increasing biosynthesis of cytoprotective prostaglandins. Accordingly, adult anesthetized rat stomachs were pretreated for 30 min with either topical 1 mM arachidonic acid, docusahexaenoic acid or eicosatrienoic acid prior to injury with topical 5 mM acidified taurocholate. In a second set of experiments using a similar protocol, the role of prostaglandins was evaluated by giving indomethacin (5 mg/kg/sc) 30 min prior to fatty acid pretreatment. Mucosal injury was assessed by measuring net transmucosal ion fluxes, the appearance of DNA into the gastric lumen, and histology. Gastric luminal PGE2 content was determined by radioimmunoassay. Pretreatment with topical arachidonic acid, but not docusahexaenoic acid or eicosatrienoic acid, significantly (P < 0.05) decreased bile acid induced net luminal ion fluxes, DNA accumulation and histologic injury scores, an effect negated by indomethacin. Further, pretreatment with arachidonic acid was associated with increased luminal PGE2 content, an effect also abolished by indomethacin. Thus, arachidonic acid does not act as a mild irritant, but protects the gastric mucosa from bile acid injury through a mechanism involving increased bioavailability of substrate for prostaglandin formation.
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