Gastric lesions induced by indomethacin (20 mg.kg'1 i.p.) were studied in rats after a 24 hour fast. The size of the lesions was correlated with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v administration) and with the rate of gastric emptying (determined from the phenol red concentration after its intragastric application). These changes were correlated with the prevention of gastric lesions by allopurinol (50 mg.kg'1) after a single dose or once daily for 3 days before indomethacin and by a single dose (15 000 dkg'1) of superoxide dismutase (SOD). Indomethacin significantly increases the rate of gastric emptying concomitantly with gastric vascular permeability. The pretreatment of animals with allopurinol and SOD inhibits gastric lesions as well as gastric vascular permeability without changing gastric emptying which was increased after indomethacin administration. The inhibition of gastric lesion formation and gastric vascular permeability was more marked in rats pretreated with allopurinol for 3 days when compared with rats treated with a single dose of allopurinol only. These results support the suggestion that oxygen-derived free radicals contribute to the pathogenesis of indomethacin-induced gastric lesions.
Stomach lesions induced by indomethacin (20 mg.kg'1 i.p.) and ethanol (1 ml 95 % intragastrically) were studied after a 24 hour fast in rats which had undergone sialoadenectomy. The size of the lesions was correlated with gastric HCI secretion, with gastric vascular permeability (determined from the Evans blue concentration in the stomach tissue after its i.v, administration) and with the serum gastrin level. These parameters were also studied in sialoadenectomized rats and in animals given epidermal growth factor (EOF) (50 lg.kg'1). It was found that sialoadenectomy significantly (p<0.01) raised the incidence of stomach lesions after the administration of indomethacin and also after ethanol (p<0.05). A significant increase in both basal and stimulated HCI secretion was found after sialoadenectomy. Both indomethacin and ethanol also increased gastric vascular permeability in rats not subjected to sialoadenectomy, but sialoadenectomy raised it significantly compared with the non-sialoadenectomized group. The serum gastrin levels fell after sialoadenectomy and the decrease was significant after the subsequent administration of indomethacin or ethanol.The administration of EGF to sialoadenectomized rats lowered the incidence of stomach lesions, inhibited HCI secretion and reduced vascular permeability. The lowered susceptibility of the gastric mucosa to the formation of lesions in sialoadenectomized rats given indomethacin or ethanol can be regarded as the outcome of the uptake of EGF.
The ability of stobadine to prevent gastric mucosal injury was tested in rat gastric ischaemia induced by 30 min clamping of the coeliac artery with subsequent 30 min reperfusion. Serious injury of gastric mucosa (macroscopic and microscopic) and the increase of microvascular permeability was found after ischaemia/reperfusion in rats without stobadine. After oral pretreatment with stobadine (5 mg.kg-1, 30 min before surgery), the development of gastric mucosal lesions and changes of vascular permeability were significantly decreased.
Malotilate as a synthetic substance shares comparable hepatoprotective properties with various flavonoids. The gastroprotective effect of some flavonoids prompted us to ascertain the similar effectiveness of malotilate. The possible gastroprotectivity was examined in gastric mucosal damage in rats induced by indomethacin (20 mg.kg-1) or ethanol (96 %). Oral pretreatment with malotilate (25, 50, 100, 200 and 400 mg.kg-1) reduced the extent of lesions induced by both indomethacin and ethanol. Histological analyses also revealed a mitigating effect on the severity of gastric mucosal lesions. Similar results were obtained in the group of rats pretreated with 5 mg.kg-1 indomethacin followed by oral administration of 96 % ethanol. This finding suggests that the effect of malotilate on rat gastric mucosa is independent of endogenous prostaglandin production.
Pentoxifylline pretreatment protects rat gastric mucosa against indomethacin-induced damage. Lipid peroxidation after indomethacin treatment (determined as thiobarbituric acid reactants) was significantly reduced by a single dose of pentoxifylline. The same was true for pentoxifylline administration for 6 days. There is a relationship between reduced lipid peroxidation, decreased number of circulating activated neutrophils and diminished disposition for acute gastric mucosal lesions induced by indomethacin in pentoxifylline-pretreated rats.
The correlation between serum gastrin levels and gastric acid secretion during 4 weeks of cimetidine administration (once daily) was investigated. Serum gastrin levels and gastric acid secretion were estimated on the 7th, 14th, 21st and 28th day after cimetidine administration (25 mg.kg'1, intragastrically). At the mentioned time intervals gastric acid secretion stimulated by histamine and pentagastrin was also studied. It was found that on the 14th and 21th day after cimetidine administration serum gastrin levels were significantly elevated. Basal gastric acid secretion after cimetidine administration was significantly decreased at all the observed time intervals. Histamine-stimulated gastric acid secretion was increased on the 14th, 21st and 28th day after cimetidine administration Hypoacidity was not followed at all time intervals by hypergastrinaemia (only on day 14 and 21 after cimetidine).