Elsevier

Biochemical Pharmacology

Volume 29, Issue 9, 1 May 1980, Pages 1281-1289
Biochemical Pharmacology

Research paper
Biochemical gastroprotection from acute ulceration induced by aspirin and related drugs

https://doi.org/10.1016/0006-2952(80)90286-5Get rights and content

Abstract

Adjuncts that serve as: (a) buffers to neutralize drug acidity, and/or (b) solubilizers of acidic drugs, or (c) certain nutrients (e.g. glucose, acetate), considerably reduced the gastric mucosal injury induced by orally administered aspirin (and other non-steroidal anti-inflammatory drugs) in stressed and starved rats. Gastroprotection against aspirin and related drugs was obtained by supplying the mucosa with glucose with intermediates or precursors of the tricarboxylic acid cycle (that may be absorbed directly from the gastric lumen). Glucose alone was not sufficiently gastroprotective. Gastroprotection with tricarboxylic acid cycle precursors given with glucose appears to be due to the effects of these nutrients in restoring ATP synthesis in the gastric mucosa. d-glutamate and d-aspartate were deaminated by homogenates prepared from saline-washed rat fundic mucosa (yielding α-oxo acids for the tricarboxylic acid cycle). These amino acids could be substituted for the l-forms in combination with glucose to yield gastroprotection from damage by aspirin. Studies in domestic pigs (a species with a pseudo-human stomach) established that acute and chronic oral administration of the aspirin + acetate + glucose combination (1: 3: 3 molar proportions) was less irritating to the gastric mucosa than aspirin alone. These results were confirmed in acute studies in monkeys. Sodium and potassium salts were superior to calcium and ammonium salts as the buffer component in these improved (i.e. less gastrotoxic) aspirin formulations tested in rats. Bicarbonate was not effective in preventing aspirin gastrotoxicity in stressed-sensitized rats, but is effective in non-stressed rats.

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