Fatty acid-mediated gastroprotection does not correlate with prostaglandin elevation in rats exposed to various chemical insults.

This study involved a comparison of activity of several long-chain fatty acids (arachidonic acid, dihomo-[gamma]-linolenic acid, linoleic acid, and oleic acid) for protection against gastric mucosal damage elicited by taurocholic acid, acidified aspirin, and ethanol in rats. Each damaging agent induced gastric mucosal lesions in the corpus. Mucosal damage was induced by all agents, and all fatty acids protected the gastric mucosa; however, ethanol and arachidonic acid were the most potent damaging and protecting agents, respectively. Maximally protective doses for prevention of taurocholic acid-induced damage by arachidonic, dihomo-[gamma]-linolenic, linoleic, and oleic acids were 50, 200, 100, and 200 mg/kg, respectively; however, 10 mg/kg arachidonic acid reduced lesion length by > 50%, whereas minimally effective doses of the other fatty acids were > or = 50 mg/kg. Similar potency differences were observed for fatty acid protection against acidified aspirin-induced gastric damage. Although all the fatty acids reduced macroscopic damage, histologic studies showed they did not totally eliminate surface mucosal damage. Microscopic analysis showed that treatment with dihomo-[gamma]-linolenic acid or oleic acid attenuated depletion of neutral and acidic glycoproteins from the mucus neck cells of the gastric mucosa in response to exposure to taurocholic acid. Despite having similar gastroprotective activity, arachidonic, dihomo-[gamma]-linolenic, linoleic, and oleic acids had very dissimilar abilities to elevate gastric mucosal E-series prostaglandins. Both arachidonic and dihomo-[gamma]-linolenic acids elevated E-series prostaglandins, but arachidonic acid had 2-5-fold greater gastroprotective potency. Furthermore, oleic and linoleic acids, which had protective potency similar to that dihomo-[gamma]-linolenic acid, did not significantly elevate prostaglandins. These studies failed to demonstrate an absolute correlation between prostaglandin elevation and gastroprotection. The results of this investigation suggest that prostaglandin elevation, although associated with gastroprotection, does not appear to be the sole mechanism for fatty acid-mediated protection of rat gastric mucosa.