Electronmicroscopic observations on the effects of orally administered aspirin and aspirin-bicarbonate mixtures on the development of gastric mucosal damage in the rat.

Abstract

SUMMARYThe effects of administering a single dose of (200 mg to 50 mg/kg body weight) aspirin or an equimolar mixture of aspirin (200 mg/kg body wt) with sodium bicarbonate on the fine structure of the rat gastric mucosa were investigated in order to establish the role of particles of the drug in the development of gastric damage. The sequence of cellular events involved in the development of a lesion and the influence of short-term starvation were also investigated. Aspirin-bicarbonate solutions produced much less damage in starved rats than aspirin suspensions given at low (50 mg/kg body weight) or high therapeutic doses (200 mg/kg body weight). Also, when non-starved rats were given 200 mg/kg aspirin, only slight damage was observed. The presence of particles of the drug in intimate contact with the mucosa is thus important in the development of gastric damage. A sequence of events with time involving direct physical exfoliation of mucosal cells and selective structural damage to parietal cells followed by structural damage indicative of a disturbance to oxidative and biosynthetic functions in cells near the developing erosion was observed. The implications of these results on the development of aspirin-induced lesions are discussed.

A synergistic interaction between aspirin, or other non-steroidal anti-inflammatory drugs, and stress which produces severe gastric mucosal damage in rats and pigs

“…In this respect the rat is a very useful species to study the development of gastric mucosal damage as the damage is obviously confined to the acid-secreting area of the stomach. This indicates that the property of acidity and the existence of a susceptible tissue, well known factors in the development of aspirininduced damage [11,13], are also major factors in the development of damage by aspirin + stress.…”

“…The animals were dosed orally with aspirin B.P. or other non-steroidal anti-inflammatory or analgesic drugs (as listed in Table 3) according to procedure employed previously [11]. Control animals were dosed with 1 ml H20 and the drugs were given as 1 ml suspensions in H20.…”

The Propionic Acids. Gastrointestinal Toxicity in Various Species

“…The necrotic foci were typically yellow and were found in the wall of the jejunum and ileum. It is interesting that gastric lesions were not apparent, since all four compounds have been shown to produce gastric toxicity experimentally (6,8). The fact that food was made available shortly after drug administration and the possibility that the stomachs may not have been completely empty at the time ofdrug administration may have been causative factors.…”

“…ASA is efficacious (3) and inexpensive, but it also has liabilities. These liabilities, including gastrointestinal intolerance and irritation (6,8), have led to the development of the numerous nonsteroidal anti-inflammatory drugs (NSAID) that are either available, or under evaluation, today. However, many of these M A I D also have liabilities, including gastrointestinal irritation.…”

Changes of Gastric Mucus Glycoproteins with Aspirin Administration in Rats

“…Many studies have been reported on the morphological and histochemical changes in the gastric mucosa associated with the prog ress of experimental gastric ulcers [4,6,[9][10][11]. However, little work has been done on the biochemical aspects of these changes.…”