Surface epithelial cell damage induced by restraint and water-immersion stress in rats. Effects of 16,16-dimethyl prostaglandin E2 on stress-induced gastric lesions.

Abstract

Abstract-The time-course of gastric mucosal surface epithelial cell damage and macroscopically visible lesions in response to restraint and water-immersion stress (22°C) in rats was examined, and the effects on it of 16,16-dimethyl prostaglandin E 2 (dmPGE2) were compared with those of papaverine, timoprazole and atropine.The stress produced surface epithelial cell damage prior to visible lesion, the former increasing in severity with time and reaching a plateau 60 min later, by which time exfoliation of surface epithelial cells was observable along the mucosal folds. In contrast, macroscopically visible lesions appeared 2 hr after stress, and severity continued to increase with time. Pretreatment injections (s.c.) of dmPGE2 (3, 30 icg/kg), papaverine (100 mg/kg) and atropine (1 mg/kg) protected the surface cells against stress (1 hr)-induced damage, and inhibited visible lesion formation after 4 hr stress. Timoprazole (30 mg/kg, s.c.) did not protect the surface cells, but did markedly inhibit visible lesion formation. dmPGE2, papaverine and atropine, but not timoprazole, inhibited stress-induced increases in gastric contractions. dmPGE2, timoprazole and atropine, but not papaverine, inhibited acid secretion in stress-conditions. These results indicated that stress induced damage to the gastric mucosa within 1 hr due to increased gastric contractions, and the surface epithelial cell damage developed into macroscopically visible lesions in the presence of acid, and that dmPGE2 protected the surface epithelium against stress-induced damage probably by inhibiting gastric contractions.

Effects of MCI-727, a New Antiulcer Agent, on Various Gastric and Duodenal Lesions in Experimental Animals.

“…For example, Mersereau and Hinchey (19) and Takeuchi et al (20) suggested that gastric hypermotility might be a major factor in the genesis of gastric lesions induced by indomethacin, by showing the close correlation between the lesion index and the motility index. Similar hypotheses have also been reported in other experimental ulcer models, including water-immersion stress-and various necrotizing agent-induced gastric lesions (13,21,22). Moreover, some antiulcer drugs such as beguhexate•CD and secretin were reported to possess inhibitory effects on gastric motility in normal rats or humans (23)(24)(25).…”

Gastric Mucosal Protection Induced by Restraint and Water-Immersion Stress in Rats

“…Furthermore, electrical stimulation of vagus nerves (0.2 mA, 2 msec, 5 Hz, 10 min) produced gastric surface epithelial cell damage (15), and, in the present study, afforded similar protection against acidified ethanol as observed after stress. The surface epithelial cell damages induced by stress and vagal nerve stimulation resulted from gastric hypercontractions, be cause pretreatments with drugs that inhibited the gastric hypercontraction induced by stress and vagal nerve stimulation protected the cells against each type of damage (9,15). These results taken together indicate that the surface epithelial cell damage due to vagal overac tivity and consequent gastric hypercontrac tions may be an obligatory process for the appearance of mucosal protection by restraint and water-immersion stress.…”

“…In the present study, 1 -hr stress-loading, vagal nerve stimu lation and atropine significantly reduced the staining of gastric mucosa with dye. Since atropine inhibits stomach contractions (9), it would reasonable that this agent strongly reduces the mucosal folds and shows the protective effect against ethanol injury. How ever, in the present study, both stress and vagal nerve stimulation markedly increased stomach contractions, yet significantly re duced the mucosal folding.…”

“…The gastric surface epithelial cell damage in response to the 1-hr stress was found to be due to increased gastric contrac tions via vagal overactivity inasmuch as the cell damage did not occur in the rats pre treated with atropine or the antispasmodic agent papaverine (9). The common character istic of mild irritants in association with their adaptive mucosal protection is damage to the surface epithelium which has been demon strated by histochemistry (10)(11)(12) and gastric mucosal potential difference (12), and vagal innervation is essential for adaptive protection by mild chronic restraint stress (8).…”

Prickly Pear Cactus (Opuntia ficus indicavar.saboten) Protects Against Stress-Induced Acute Gastric Lesions in Rats

“…saboten against stress-induced gastric lesions, since it is a widely used experimental model to induce acute stress ulcers in rats and is known for its reliable reproducibility. 19 A large number of natural products have been evaluated for their antiulcler effects while searching for possible candidates for new drugs or functional foods. 20 Opuntia species are also well known for its gastroprotective activities as demonstrated in various experimental models.…”