Role of taurocholic acid in production of gastric mucosal damage after ingestion of aspirin.

The mechanism of the protective actions of sucralfate against ethanol-induced gastric mucosal damage in the rat has been investigated. In particular, the role of prostaglandins as mediators of such protection was assessed. Oral administration of sucralfate at a dose causing a significant reduction of ethanol-induced gastric damage (500 mg/kg) did not significantly alter gastric 6-ketoprostaglandin F1α synthesis. Pretreatment with indomethacin at a dose that inhibited gastric cyclooxygenase activity by an average of 88% did not affect the protective actions of sucralfate. To further investigate the mechanism of action of sucralfate, an ex vivo gastric chamber model was used in which sucralfate could be applied to only one side of the mucosa. Sucralfate did not affect gastric prostaglandin synthesis, but did cause a significant increase in leukotriene C4 synthesis, a fall in transmucosal potential difference, and a significant decrease in gastric myeloperoxidase activity on the side exposed to sucralfate. These observations suggest that sucralfate has an irritant action on the mucosa. The release of mediators in response to such irritation may play an important role in the protective action of sucralfate. The present study supports the hypothesis that prostaglandins do not mediate the protection afforded by exposure to sucralfate.

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Fatty Acid-mediated Gastroprotection Does Not Correlate with Prostaglandin Elevation in Rats Exposed to Various Chemical Insults

Veterinary Pathology ◽

10.1177/030098589403100608 ◽

1994 ◽

Vol 31 (6) ◽

pp. 679-688 ◽

Cited By ~ 2

Author(s):

K. G. Mandel ◽

T. A. Bertram ◽

M. K. Eichhold ◽

S. C. Pepple ◽

M. J. Doyle

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Oleic Acid ◽

Fatty Acid ◽

Gastric Mucosa ◽

Linolenic Acid ◽

Mucosal Damage ◽

Taurocholic Acid ◽

Gastric Mucosal Damage ◽

Gastric Mucosal Lesions

This study involved a comparison of activity of several long-chain fatty acids (arachidonic acid, dihomo-[γ]-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-[γ]-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 ≥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-[γ]-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-[γ]-linolenic, linoleic, and oleic acids had very dissimilar abilities to elevate gastric mucosal E-series prostaglandins. Both arachidonic and dihomo-[γ]-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-[γ]-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.

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