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 prevents the formation of acute gastric lesions induced by various ulcerogens and enhances the healing of chronic gastroduodenal ulcerations, but the mechanism of these effects has not been fully explained. This study was designed to determine the importance of intragastric pH in the sucralfate-induced gastroprotection against 100% ethanol, acidified aspirin, taurocholate, or stress, and in the healing of chronic gastroduodenal ulcerations induced by acetic acid. Sucralfate acidified to pH 2.0 showed significantly stronger protective activity against all four irritants, its protective potency against 100% ethanol being about eight times greater and the duration of the protection about four times longer than those obtained with sucralfate at its pH of 5.0. Pretreatment with indomethacin to suppress mucosal generation of prostaglandin or the removal of salivary glands to eliminate the endogenous source of epidermal growth factor failed to affect sucralfate-induced gastroprotection. In contrast, the rate of healing of chronic gastric ulcerations was significantly delayed by indomethacin or sialoadenectomy; but sucralfate enhanced the healing, and a marked inhibition of gastric acid secretion by ranitidine did not eliminate this enhancement. We conclude that the protective activity of sucralfate depends on the presence of acid milieu in the stomach, but that the ulcer-healing effects of this drug occur even after a marked inhibition of gastric acid secretion.
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PMID:Role of acid milieu in the gastroprotective and ulcer-healing activity of sucralfate. 188 4

Epidermal growth factor (EGF) has been shown to enhance healing of experimental gastric ulcers when given subcutaneously or orally in the drinking water. This effect of EGF occurs without reducing gastric acid secretion. On the other hand, EGF reportedly is excreted rapidly from gastric lumen when administered by intragastric bolus. This suggests that further stimulation of ulcer healing may be expected if EGF is given with an acid-suppressive agent or with an agent allowing EGF to remain in rat gastric lumen at high concentrations. In the present study, EGF administered by gastric intubation at a dose of 10 micrograms/kg, which is three times smaller than reported in previous studies, was evaluated for its effect on acetic acid-induced rat gastric ulcers in combination with sucralfate or omeprazole. Sucralfate is well known selectively to bind proteins covering the ulcer base, and omeprazole is a potent acid-suppressive agent. Prior to the study of combined EGF and sucralfate, oral sucralfate was confirmed to allow endogenous gastric EGF and mouse EGF given exogenously to remain at high concentrations in gastric contents and tissues. EGF and sucralfate (2 g/kg/day) given alone failed to stimulate ulcer healing in submandibularectomized rats (SMR rat) whose endogenous gastric EGF was depleted. However, the combination of both drugs administered at the same doses significantly accelerated ulcer healing in the SMR rat. Omeprazole (200 mg/kg/day) significantly enhanced ulcer healing regardless of removal of the submandibular glands. The combination of EGF and omeprazole further stimulated ulcer healing in the SMR rat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of epidermal growth factor in combination with sucralfate or omeprazole on the healing of chronic gastric ulcers in the rat. 221 45

Sucralfate exhibits gastroprotective properties in laboratory animals and enhances the healing of chronic gastroduodenal ulcers, but the mechanisms of these actions have not been entirely elucidated. The present study was designed to determine whether or not epidermal growth factor (EGF), which also has gastroprotective and ulcer-healing properties, contributes to the action of sucralfate in rat stomach. It was confirmed that sucralfate, like 16,16-dimethyl prostaglandin E2, protects the gastric mucosa against ethanol damage and increases mucosal generation of prostaglandins. Removal of the endogenous source of EGF (sialoadenectomy) did not abolish the protective and prostaglandin-stimulating effects of sucralfate. Exogenous EGF and 16,16-dimethyl prostaglandin E2 were also protective in rats with intact and removed salivary glands. Sucralfate, like EGF, enhanced the healing of chronic gastric and duodenal ulcerations induced by serosal application of acetic acid. Sucralfate was found to bind EGF in a pH-dependent manner and to accumulate it in ulcer areas. Thus, the peptide is available locally in high concentrations to accelerate tissue repair and the healing process in ulcerated mucosa. The ulcer-healing effects of sucralfate were reduced with sialoadenectomy and partially restored with oral administration of EGF. It was concluded that EGF is not essential for the gastroprotection induced by sucralfate, but seems to play an important role in the ulcer-healing action of this drug.
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PMID:Epidermal growth factor in the gastroprotective and ulcer-healing actions of sucralfate in rats. 278 72

The effects of oral sucralfate, a basic aluminum salt of sulfated disaccharide, on various experimental gastric lesions and on gastric secretion were studied in rats. Sucralfate at 300 mg/kg potently inhibited the development of Shay ulcers and indomethacin- and aspirin-induced erosions. The drug at 1000 mg/kg also potently inhibited histamine-induced erosions. Water-immersion stress-induced erosions were inhibited with 1000 mg/kg of the drug, but the degree of inhibition was weaker than that seen in other types of erosion formation. Sucralfate at 1000 mg/kg given twice daily for 14 days significantly accelerated the spontaneous healing of acetic acid-induced ulcers. Sucralfate at over 300 mg/kg tended to increase the volume of gastric juice but had an insignificant effect on acid and pepsin output of pylorus-ligated rats. As a whole, the effects of sucralfate on experimental gastric lesions appear to be much more potent than Maalox, propantheline bromide, and cimetidine. The mechanism of action of sucralfate remains to be determined.
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PMID:Effects of an antiulcer drug, sucralfate (a basic aluminum salt of sulfated disaccharide), on experimental gastric lesions and gastric secretion in rats. 668 79

14C-Sucralfate, a basic aluminum salt of 14C-sucrose sulfate, or potassium 14C-sucrose sulfate was administered orally to rats with acetic acid-induced gastric ulcer. The radioactivities representing specific binding of the sucrose sulfate moiety were found significantly higher in ulcer sections of the stomach, with the mean within-animal ulcer/non-ulcer ratio attaining 6, 7, 12 and 2.5, respectively, at 1, 3, 6 and 24 h after 14C-sucralfate administration. Microautoradiography provided direct in vivo evidence for binding of the 14C-sucrose sulfate moiety to exuded proteins resulting in effect in formation of a pepsin-resistant barrier over the surface of an ulcer crater. No comparable findings were obtained in the area of normal mucosa. The administration of 14C-sucralfate was associated with much greater and longer-sustained binding to the ulcer lesion and retention in the stomach and duodenum than simple administration of the soluble potassium salt. These findings not only demonstrate therapeutically significant effects of basic aluminum compoundation but also substantiate likely differences from pepsin inhibitors such as amylopectin sulfate in terms of presence or absence of adhesiveness, local barrier effects, and long duration of actions.
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PMID:Selective binding of sucralfate to ulcer lesion. II. Experiments in rats with gastric ulcer receiving 14C-sucralfate or potassium 14C-sucrose sulfate. 689 77

Sucralfate, a basic aluminum salt of sucrose sulfate, has been shown to accelerate the healing of peptic ulcers. We studied its binding to normal and ulcerated rat mucosa after gastric and duodenal ulcers had been induced by acetic acid. Sucralfate adhered to ulcerated mucosa for over 6 hours, in the presence and absence of antacid. Food, eaten 1 hour after sucralfate administration, did not appear to alter its selective binding to ulcer sites, but did reduce the amount of sucralfate bound to healthy tissue. The results suggest that sucralfate has a greater affinity for ulcerated mucosa than normal mucosa.
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PMID:Effect of food and antacid on binding of sucralfate to normal and ulcerated gastric and duodenal mucosa in rats. 689 42

The study was designed to determine the gastroprotective and ulcer healing efficacy of basic transforming growth factor (bFGF) and to assess whether this peptide contributes to the action of sucralfate on the rat stomach. Application of human recombinant bFGF (1-100 micrograms/kg/hour subcutaneously) failed to affect the formation of acute gastric lesions induced by 100% ethanol and acidified aspirin but reduced the stress induced by gastric lesions. Sucralfate (100-200 mg/kg given orally) protected gastric mucosa against the ethanol, aspirin, and stress induced acute gastric lesions but the addition of bFGF (100 micrograms/kg subcutaneously or intragastrically) failed to affect sucralfate induced protection against ethanol or aspirin but increased that against stress. Administration of bFGF (3-300 micrograms/kg/day) by an intragastric or an intraperitoneal route or sucralfate (400 mg/kg/day) orally to rats with acetic acid induced gastric ulcers, enhanced the healing rate of these ulcers during seven day treatment in a dose dependent manner. This was accompanied by a pronounced increase in the number of capillaries and myofibroblasts and in DNA synthesis and DNA and RNA concentrations in the granulation tissue in the ulcer area. [125I]bFGF (1 microCi) applied subcutaneously or intragastrically accumulated in two to threefold higher amounts in the ulcer area than in the intact mucosa, particularly in rats treated with sucralfate. Concurrent treatment with indomethacin (2 mg/kg intraperitoneally) delayed ulcer healing and reduced the binding of labelled bFGF to the ulcer area, angiogenesis, and DNA synthesis by sucralfate. Addition of [125I]bFGF to sucralfate at various pHs resulted in the coprecipitation of bFGF by sucralfate in a pH dependent manner from about 10% at pH 7.0 to 90% at pH 1.5. Thus bFGF shows little protective activity and is not essential for gastroprotection afforded by sucralfate but plays an important part in healing of gastric ulcers possibly due to its growth promoting and angiogenic actions.
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PMID:Fibroblast growth factor in gastroprotection and ulcer healing: interaction with sucralfate. 834 73

We examined the effect of sucralfate on spontaneous and delayed healing of experimental gastric ulcers and the underlying mechanism of action. Gastric ulcers were produced 5 days after submucosal injection of 20% acetic acid (0.03 ml) into the antral-oxyntic border of rat stomachs. To delay the healing of ulcers, indomethacin was administered s.c. at 1 mg/kg once daily for 4 weeks from 5 days after the acid injection. Sucralfate, administered p.o. three times daily, significantly accelerated the spontaneous healing of ulcers, the healing rates being 13.7%, 43.7% and 47.1% with 100 mg/kg, 300 mg/kg and 600 mg/kg, respectively. In addition, the drug also significantly prevented the delay in ulcer healing caused by indomethacin, the preventive rates being 56.6% and 83.9% with 300 mg/kg and 600 mg/kg, respectively. Sucralfate, even at 1000 mg/kg, had no effect on the mucosal prostaglandin E2 (PGE2) level around the ulcers and did not affect the reduced PGE2 content caused by indomethacin. A single dose of sucralfate significantly increased the volume and the pH of the gastric contents in a dose-dependent manner, the effects persisting for up to 8 hr. These results suggest that the mechanism by which sucralfate accelerates the healing of gastric ulcers is unrelated to endogenous PGs but related to the acid-neutralizing activity.
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PMID:Effect and mechanism of sucralfate on healing of acetic acid-induced gastric ulcers in rats. 835 48

Sucralfate is a drug used in the treatment of gastric and duodenal ulcer; it is cytoprotective and able to increase the bioavailability of several growth factors, modulating the wound healing process. In this study we tested the possible therapeutic effect of Sucralfate in the treatment of ulcerative lesions occurring in uterine cervix; to investigate such effect we used an experimental rat model of cervicitis in which the uPAR and EGFR expression were evaluated. Cervicitis was induced in wild and ovariectomized Wistar female rats by an acetic acid-soaked tampon. The animals were divided into two main groups (4 and 7 days) and Sucralfate was administered topically until the day they were sacrificed. In order to distinguish physiological and drug-induced healing, quantitative and qualitative uPAR and EGFR expression were evaluated by using Western blot and Immunohistochemistry techniques. Western blot analysis demonstrated an increased expression of both receptors after 4 days from wounding in wild and ovariectomized animals. In particular in ovariectomized animals the expression of uPAR and EGFR increased after 4 days while it reduced following the administration of Sucralfate. In wild rats the same was observed for uPAR expression, while EGFR was different; in fact, its expression increased significantly at day 4 in the animals treated with the drug and only at day 7 in those untreated. Immunohistochemistry highlighted a noteworthy epithelial colocalization of EGFR and uPAR after 4 days in the animals treated with Sucralfate. We conclude that Sucralfate can promote the healing of ulcerative cervicitis and moreover, it reduces the normal healing time because of its modulatory property on uPAR and EGFR expression.
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PMID:Sucralfate modulates uPAR and EGFR expression in an experimental rat model of cervicitis. 1883 33