Section 5
Chapter 4,788

Assessment of gastric mucosal damage: comparative effects of aspirin and fenclofenac on the gastric mucosa of the guinea pig

Garner, A.

Toxicology and Applied Pharmacology 42(3): 477-486


ISSN/ISBN: 0041-008X
PMID: 304613
DOI: 10.1016/s0041-008x(77)80032-x
Accession: 004787210

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Gastric mucosal damage in the guinea pig was assessed by measuring the concentrations of blood and DNA in gastric washings and by morphological examination of the mucosa. Exposure of the mucosa to aspirin in suspension at pH 2.0 for 10 min caused an increase in the rate of accumulation of DNA in the washings together with gastric bleeding and the formation of macroscopically visible erosions. Under similar conditions of administration fenclofenac (2-(2,4-dichlorophenoxy)phenylacetic acid) had little effect. In solution at pH 7.4 aspirin-induced mucosal damage was minimal; fenclofenac produced a large increase in the rate of accumulation of DNA in the gastric washings, but only slight blood loss and visibly detectable damage. Microscopical examination of the mucosa after aspirin at pH 2.0 revealed the presence of deep focal erosions but, at pH 7.4, only a few shallow erosions were observed. The appearance of the mucosa after fenclofenac at pH 2.0 was similar to that of control animals. At pH 7.4 the drug caused widespread exfoliation of surface mucosal cells but no penetrating erosions of the type seen after aspirin. Estimation of the DNA concentration in gastric washings was a sensitive index of mucosal damage, detecting superficial and focal cell loss. Damage was detected macroscopically only when the erosions were deep or accompanied by bleeding.

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