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.
The role of afferent sensory neurones in gastric mucosal protection is discussed. The principal effects of substance P and capsaicin on gastric motility and mucosal blood flow are taken in correlation with gastric mucosal injury. It seems likely that the protective effect of sensory neuropeptides is dependent on gastric mucosal blood flow and is mediated through the nitric oxide-generating system and partly the prostaglandins. The interaction between these two systems and the primordial effect of one of them on gastric mucosal blood flow and mucosal integrity after neuropeptide release is still not clear.