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 fat ty acids (arachidonic acid, dihomo-[gamma]-linolenic acid, linoleic ac id, and oleic acid) for protection against gastric mucosal damage elic ited 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 g astric mucosa; however, ethanol and arachidonic acid were the most pot ent damaging and protecting agents, respectively. Maximally protective doses for prevention of taurocholic acid-induced damage by arachidoni c, dihomo-[gamma]-linolenic, linoleic, and oleic acids were 50, 200, 1 00, and 200 mg/kg, respectively; however, 10 mg/kg arachidonic acid re duced lesion length by > 50%, whereas minimally effective doses of the other fatty acids were greater than or equal to 50 mg/kg kg. Similar potency differences were observed for fatty acid protection against ac idified aspirin-induced gastric damage. Although all the fatty acids r educed macroscopic damage, histologic studies showed they did not tota lly 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 cel ls 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 abili ties to elevate gastric mucosal E-series prostaglandins. Both arachido nic and dihomo-[gamma]-linolenic acids elevated E-series prostaglandin s, but arachidonic acid had 2-5-fold greater gastroprotective potency. Furthermore, oleic and linoleic acids, which had protective potency s imilar to that dihomo-[gamma]-linolenic acid, did not significantly el evate prostaglandins. These studies failed to demonstrate an absolute correlation between prostaglandin elevation and gastroprotection. The results of this investigation suggest that prostaglandin elevation, al though associated with gastroprotection, does not appear to be the sol e mechanism for fatty acid-mediated protection of rat gastric mucosa.