SUMMARY Quantitative changes of gastric mucosal glycoproteins with the gastric damage induced by acetylsalicylic acid (aspirin) in rat have been studied. Gastric injury was easily observed macroscopically within one hour after the oral administration of aspirin. The most striking changes occurred at five hours, and the injury was overcome within nine hours after dosing. The glycoproteins extracted from rat stomach with Tris buffer containing Triton X-100 were fractionated on Bio-Gel A-1 5 m column chromatography and divided into three fractions. Received for publication 30 November 1979 permitted free access to water. Aspirin was suspended in 05% carboxymethyl cellulose at a concentration of 50 mg per ml. The aspirin suspension was administered orally as a single dose of 300 mg per kg body weight, and the animals were killed by exsanguination from the carotid artery at time intervals of one, two, three, five, seven, and nine hours after dosing. The stomachs were excised immediately and cut along the greater curvature. The stomach contents were washed with phosphate buffered saline, and the surface of the mucosa was wiped with soft tissue paper. In order to assess the mucosal damage macroscopical observation was carried out.13 Control rats were treated as described above except for the administration of aspirin.Portions of the glandular stomach were selected macroscopically and excised, and the tissues were lyophilised. The lyophilised three or four stomachs were pooled, weighed, and ground in a mortar. The resultant powder was suspended in 0.05 M Tris-HC1 buffer, pH 7-2, containing 2% Triton X-100 (1-5 ml/100 mg dry tissue) and homogenised by hand in a Potter-Elvehjem glass homogeniser. erosions and their size, and the number of animals with lesions present, is shown in Table 1. No macroscopical damage was observed in the forestomach. Haemorrhagic erosions and linear ulcers in the glandular stomach were visible in six of the 23 experimental stomachs within one hour after aspirin administration. The extent of damage was increased with the passage of time. The most striking changes occurred five hours after dosing. A gradual return to the control situation was observed later. The injury had nearly abated macroscopically within nine hours.The wet weight of whole stomach per rat was unchanged with or without aspirin treatment (600 ±+20 mg). The weight ratio of glandular stomach to forestomach was about 3:1. The average weight of dried glandular stomach per rat was also compared with the aspirin treated and control rats. No dif-

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The qualitative changes of gastric mucus glycoproteins occurring after aspirin dosing in rats were further investigated. Mucus glycoprotein contents of test animals were 55 and 53% of the control value at 3 and 7 h after dosing, respectively. The glycoproteins were further fractionated by CM-Sepharose CL-6B chromatography. 5 fractions were separated, 1 unadsorbed (fraction 1) and 4 adsorbed (fractions 2–5). Ratios of the major fractions 1:2:4 were 36:47:17 for control, 40:35:25 3 h after aspirin dosing, and 47:33:20 7 h after aspirin administration. Fractions 1, 2, and 4 corresponded to sulfomucin and sialomucin (relatively high content of sialic acid), sialomucin, and neutral mucin, respectively. While the absolute amount of each mucus glycoprotein fraction decreased with aspirin administration, the diminution of fraction 2 was distinct.

The efficacy of two anti-ulcer drugs, Cimetidine and Cetraxate, on the mucus glycoproteins of gastric mucosa in the aspirin-induced gastric damage was studied in rats. Simultaneous or previous oral administration of Cimetidine or Cetraxate with aspirin reduced the diminution of the mucus glycoproteins which was occurred by aspirin administration. The recovery of the content of mucus glycoprotein in drug dosed rats occurred within 3 h after aspirin dosing and was nearly 90% of control at 5 h in all cases. Single administration of Cetraxate or Cimetidine produced an increase in the mucus glycoprotein content greater than that of the untreated control. Although a macroscopical method for the measurement of gastric damage was applied to this work, neither erosions nor linear ulcers were observed in all cases except the single administration of aspirin. The biochemical method used should be able to assess the efficacy of drugs on the mucosal lesion which cannot be expressed as the ulcer index.

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