Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00446 (Sucralfate)
 278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sucralfate is a nonsystemic agent that is effective in protecting the gastroduodenal mucosa against injury. In addition, sucralfate is effective in the healing of acute duodenal and gastric ulceration, the therapy of esophagitis, and the prevention of ulcer recurrence. The mechanisms responsible for sucralfate's successful protective and therapeutic actions include the adsorption of pepsin and bile acids, the stimulation of bicarbonate and mucus secretion, and stimulation of endogenous synthesis of prostaglandins. When sucralfate is given to experimental animals or humans, it stimulates endogenous synthesis and release of prostaglandin E2 and inhibits thromboxane release. Pretreatment of animals with the cyclooxygenase inhibitor indomethacin results in a marked decrease in the protective effect of sucralfate against alcohol injury. Sucralfate also increases epidermal growth factor binding to ulcerated areas and stimulates macrophage activity. In addition, sucralfate stimulates endogenous sulfhydryl compounds. At the microscopic level sucralfate protects the vascular integrity of the mucosa and the mucosal proliferative zone. It also stimulates epithelial cell restitution and stimulates cell proliferation. The administration of sucralfate before acute injury results in decreased depth and extent of injury and in acceleration of healing. Because of sucralfate's ability to stimulate the protective and reparative mechanisms of the gastric and duodenal mucosa, it is an important nonsystemic agent for the therapy and prevention of peptic ulceration.
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PMID:The protective and therapeutic mechanisms of sucralfate. 219 Mar 4

The protective effect of sucralfate against gastric and intestinal mucosal damage was studied in rats. Sucralfate (125 mg) significantly reduced gastric mucosal lesion formation induced by s.c. administration of indomethacin (30 mg/kg) or intragastric administration of aspirin (100 mg/kg), HCl (0.6 N), NaOH (0.2 N) or sodium taurocholate (30 mM). Furthermore, when given in three doses of 125 mg each, sucralfate significantly decreased the development of small intestinal lesions induced by indomethacin in the re-fed rat. Gastric mucosal cyclooxygenase activity in sucralfate-treated rats expressed as prostaglandin E2 formation--388 +/- 140 (ng/g wet weight; mean +/- SE)--was significantly higher (P less than 0.01) than its activity in the control--264 +/- 62 (ng/g wet weight). Sucralfate also slightly, but significantly, decreased indomethacin-induced gastric mucosal cyclooxygenase inhibition. Intestinal mucosal cyclooxygenase activity was not affected by sucralfate. The results suggest that gastric and intestinal mucosal damage induced by various ulcerogens is significantly reduced by sucralfate. Sucralfate-induced stimulation of endogenous gastric mucosal prostanoid formation may in part explain its effective protective properties.
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PMID:Sucralfate protection against gastrointestinal damage: possible role of prostanoids. 309

The mechanism of the protective actions of sucralfate against ethanol-induced gastric mucosal damage in the rat has been investigated. In particular, the role of prostaglandins as mediators of such protection was assessed. Oral administration of sucralfate at a dose causing a significant reduction of ethanol-induced gastric damage (500 mg/kg) did not significantly alter gastric 6-ketoprostaglandin F1 alpha synthesis. Pretreatment with indomethacin at a dose that inhibited gastric cyclooxygenase activity by an average of 88% did not affect the protective actions of sucralfate. To further investigate the mechanism of action of sucralfate, an ex vivo gastric chamber model was used in which sucralfate could be applied to only one side of the mucosa. Sucralfate did not affect gastric prostaglandin synthesis, but did cause a significant increase in leukotriene C4 synthesis, a fall in transmucosal potential difference, and a significant decrease in gastric myeloperoxidase activity on the side exposed to sucralfate. These observations suggest that sucralfate has an irritant action on the mucosa. The release of mediators in response to such irritation may play an important role in the protective action of sucralfate. The present study supports the hypothesis that prostaglandins do not mediate the protection afforded by exposure to sucralfate.
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PMID:Effects of sucralfate on gastric prostaglandin and leukotriene synthesis: relationship to protective actions. 341 36