Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and ?-catenin in colonic mucosa without fecal stream.

PURPOSE: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. METHODS: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. RESULTS: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. CONCLUSIONS: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and Β-catenin in colonic mucosa without fecal stream

ABSTRACT Purpose: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. Methods: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. Results: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. Conclusions: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Selective binding of sucralfate to endoscopic mucosal resection-induced gastric ulcer: evaluation of aluminium adherence.

We evaluated the effect of sucralfate in patients with early gastric cancer in endoscopic mucosal resection (EMR)-induced gastric ulcers, and in rats with acetic acid-induced ulcers, by measuring concentrations of aluminium adhering to mucosal lesions. Twenty-two patients who underwent EMR received sucralfate with or without ranitidine and were examined endoscopically after 1 week, 2 weeks and 3 weeks. Gastric juice pH and concentration of aluminium in samples of ulcerated and normal mucosa were measured at various time-points. Good ulcer healing was observed in all patients. Significantly higher concentrations of aluminium were found in ulcerated tissue compared with normal mucosa. This selective binding of sucralfate was even found 12 h after drug administration and was confirmed in acetic acid-induced ulcers in 40 rats. Neutral rather than acid gastric juice was observed up to 12 h after the administration of sucralfate alone. These results suggest that sucralfate with or without ranitidine may contribute to the healing of EMR-induced ulcers by selectively binding to lesions.

Effect of drying methods on retention of moist sucralfate gel properties.

The aim of this work was to find a drying procedure for moist sucralfate gel capable of producing dried sucralfate gel that retains the original gel properties of bioadhesion, rheology, and micromeritics. Spray-drying and microwave-drying procedures were employed. Mannitol was used as a gel-protective substance during the drying processes. The spray drying of moist sucralfate gel gave rise to a powder whose water suspensions showed significantly reduced viscosity. The bioadhesion of spray-dried sucralfate gel was strongly reduced by drying. When mannitol was used as a gel protector, the spray-dried sucralfate in part maintained the original bioadhesion of moist sucralfate gel. The preparation of a dried sucralfate gel retaining the bioadhesion characteristics, avoiding the use of mannitol, was made possible using the microwave-drying procedure. The microwave-dried product possesses a granular morphology suitable for direct compression because it is a free flowing and strongly coherent granular powder.

The anti-ulcer drug sucralfate does not affect gastric nicotine levels.

OBJECTIVE: It has been claimed that sucralfate can overcome the negative effects of nicotine in patients with peptic ulcer disease, although the possible mechanism being unknown. This study was performed in order to test whether sucralfate was capable of binding intragastric nicotine, thus making it impossible for the substance to exert effect. METHOD: Nicotine was administered via transdermal patches or as capsules yielding gastric concentrations of 40-2980 ng.ml-1. Gastric juice aspirates (n = 9) were incubated with sucralfate, which was then separated by centrifugation, and the nicotine concentration was compared in incubated and non-incubated samples. RESULTS: A median decrease of 13% (range 0-27%) in nicotine concentration was seen after incubation with sucralfate (P = 0.01). CONCLUSION: The binding of nicotine to the precipitating agent sucralfate is not sufficient effectively to remove nicotine from the gastric juice.

The exogenous administration of basic fibroblast growth factor to regenerating skeletal muscle in mice does not enhance the process of regeneration.

The effects, in vivo, of the exogenous administration of bFGF on myogenesis of regenerating skeletal muscle was assessed either morphometrically or autoradiographically in three separate models of muscle injury in mice: crush-injured, denervated, and dystrophic (mdx) muscles. The bFGF was administered at various doses and different time schedules, sometimes in combination with heparin, into injured tibialis anterior muscles of mice. Delivery of the bFGF was either by direct intramuscular injection or by the sustained release from 888polymers (Hydron or Elvax) implanted into the muscles. The bioactivity of bFGF was confirmed in vitro by measuring its ability to stimulate the proliferation of BALB/c-3T3 fibroblasts and muscle precursor cell lines. The ability of bFGF to stimulate angiogenesis in vivo was confirmed by the implantation of controlled-release polymers containing bFGF into the normally avascular cornea of rats. No measurable effect of bFGF was seen in any of the models of skeletal muscle injury under these experimental conditions, indicating that the availability of biologically active bFGF is not a limiting factor in the regeneration of skeletal muscle following injury.

Relationship between gastroprotective effect of locally acting antiulcer agent ecabet sodium and its binding to gastric mucosa in rats. Comparison with sucralfate.

The present study was designed to examine the relationship between the gastroprotective efficacy of the locally acting antiulcer drug ecabet sodium (ecabet) against ethanol-induced gastric lesions and the amount of the drug bound to the mucosa in comparison with sucralfate in rats. Oral administration of ecabet (25-100 mg/kg) and sucralfate (25-400 mg/kg) dose dependently prevented the formation of ethanol-induced gastric lesions, and dose dependently increased the amount of each drug bound to the gastric mucosa. Pretreatment with the antisecretory agent cimetidine (200 mg/kg, per os) significantly reduced the gastroprotective effect of sucralfate in proportion to a decrease in its binding to the mucosa. The same pretreatment tended to reduce both gastroprotection by ecabet and its binding to the mucosa. In an in vitro study using an everted stomach sac, the binding of sucralfate to the mucosa was more markedly decreased than that of ecabet on increasing the pH. These findings indicate that ecabet and sucralfate protect the gastric mucosa against ethanol in proportion to the amount of each drug bound to the gastric mucosa and that the binding of these drugs to the mucosa is under the influence of intraluminal pH. However, the gastroprotective effect of ecabet seems to be less dependent on intraluminal acidity than that of sucralfate.

Aluminum absorption and excretion following sucralfate therapy in chronic renal insufficiency.

PURPOSE: To measure serum aluminum levels and urinary aluminum excretion in patients with chronic renal insufficiency (CRF) receiving therapeutic doses of sucralfate. PATIENTS: Six patients with CRF were enrolled in the study. Creatinine clearances ranged from 0.2 to 0.9 mL/second (mean +/- SD 0.40 +/- 0.25 mL/second). Seven subjects with normal renal function were also studied. METHODS: Each subject received sucralfate 1 g four times daily for 21 days. Serum and urine samples (serum only) were collected on baseline and on Days 2, (3), 8, 15, 22, (23, 24), 29, and 36. Samples were assayed by graphite furnace atomic absorption spectrophotometry. RESULTS: In CRF, serum aluminum levels (mumol/L) increased by Day 2 and remained elevated to Day 24. Urinary aluminum excretion (mumol/day) was elevated throughout the study. The elimination half-life of serum aluminum after therapeutic dosing of sucralfate was 13.1 +/- 3.1 days. In subjects with normal renal function, baseline serum aluminum levels were similar to those in CRF (0.12 +/- 0.12 versus 0.11 +/- 0.12 mumol/L), but serum aluminum levels were higher at the end of the study in CRF (Day 22, 0.24 +/- 0.17 versus 0.83 +/- 0.48 mumol/L). CONCLUSIONS: After therapeutic doses of sucralfate, significant elevations of serum aluminum levels occurred in CRF. Serum aluminum levels were higher in patients with CRF than in normal subjects. Long courses of sucralfate should be used with caution or avoided in CRF.

The effect of sucralfate on the growth of cariogenic streptococci.

Sucralfate, an aluminum salt of sucrose octasulfate, has been shown to be effective in reducing the discomfort of radiation therapy-induced oral mucositis. This study was done to determine whether sucralfate could be used as a nutritional source for dental caries-producing organisms. Three Streptococcus strains were cultured in a defined medium. Sucralfate powder was evaluated for its ability to be used as a carbohydrate food source by these organisms. The addition of sucralfate alone did not stimulate the organism's growth. The addition of sucralfate and glucose resulted in less growth than the addition of glucose alone. Increasing the sucralfate concentration from 1% to 10% in the glucose-containing cultures resulted in statistically significant growth inhibition (p less than 0.02). Sucralfate appears to have no cariogenic potential and may have some cariostatic potential.

Mucosal injury and gamma-irradiation produce persistent gastric ulcers in the rabbit. Evaluation of antiulcer drug binding to experimental ulcer sites.

A method producing persistent gastric ulcers in the rhesus monkey by combined mucosal injury and gamma-irradiation was modified and evaluated in the rabbit. gamma-Irradiation (800-1000 cGy) immediately after removal of 2-mm-diameter sections of antral mucosa resulted in ulcer craters 5-7 days later. Ulcer sites were characterized by loss of the mucosa, muscularis mucosa, and much of the submucosa. The exposed submucosa was coated with fibrin and necrotic debris infiltrated with heterophils, the rabbit equivalent of neutrophils. These ulcers strongly resemble human chronic gastric ulcers. Binding of Carafate (sucralfate; Marion Laboratories, Inc., Kansas City, MO) and Maalox (magnesia-alumina oral suspension; Wm. H. Rorer, Inc., Ft. Washington, PA) to ulcer and nearby nonulcer sites in the antrum was assessed 1 hour after drug dosing. Drug binding was determined by aluminum quantitation of stomach wall punch biopsies at necropsy. Both drugs significantly increased aluminum bound to the stomach wall compared with vehicle treatment. Significantly more antiulcer drug was bound to ulcer sites than to nearby nonulcer sites only after sucralfate administration. This model of persistent gastric ulcer should be useful to further study gastric ulcer pathogenesis and treatment.

Plasma and urine aluminium concentrations in healthy subjects after administration of sucralfate.

1. Sucralfate (basic sucrose aluminium sulphate), a topical intestinal agent, was administered in suspension or granule form to 25 healthy subjects at a total dose of 4 g day-1 for 21 days. Aluminium in plasma and 24 h urine samples was assayed before, during and after administration of sucralfate by inductively coupled plasma optical emission spectrometry. 2. Sucralfate produced significant increases in plasma and urine aluminium concentrations. On average, plasma aluminium increased from about 2 micrograms 1-1 to more than 5 micrograms 1-1 and 24 h urine aluminium increased from less than 5 micrograms to more than 30 micrograms. Both plasma and urine aluminium concentrations decreased rapidly after sucralfate was stopped. However, urinary aluminium concentrations remained higher than normal 5 and 10 days after discontinuation of sucralfate administration. Moreover subjects receiving sucralfate granules had significantly higher average urinary excretion of aluminium than subjects receiving the suspension. 3. The small but significant increase in plasma and urine aluminium following sucralfate administration in therapeutic doses may reflect intestinal absorption of aluminium. Although such absorption would appear to be moderate in healthy subjects, it is suggested that aluminium-based treatments should be used only intermittently, especially in patients with renal disorders.

Bile salt binding by maalox, sucralfate, and meciadanol: in vitro and clinical comparisons.

Inhibition of gastric acid secretion is a major factor in protecting the gastric mucosa, although other mechanisms such as bile salt binding may contribute to the protective properties of individual agents. Sucralfate, antacid (Maalox), and Meciadanol, a new flavonoid, were compared with cholestyramine resin for binding bile salts. The free, glycine, and taurine conjugates of the human bile salts, cholate, chenodeoxycholate, and deoxycholate, were incubated with each of the above. Cholestyramine resin adsorbed 91-97% of all bile salts tested. Meciadanol adsorbed all of the bile salts fairly well except for the free forms of chenodeoxycholate and deoxycholate. Meciadanol (53 to 84%) adsorbed bile salts better than sucralfate (4.2 to 61%), and significantly (P less than 0.05) better than Maalox (10 to 47%). In our in vitro studies, sucralfate was not as effective in binding bile salts as previously reported. Patients in the surgical intensive care unit were randomized prospectively to receive nasogastric instillation of Maalox, sucralfate, or Meciadanol to prevent gastrointestinal bleeding. The gastric aspirates were analyzed for bile salt concentration. The mean bile salt concentration of those treated with Maalox (0.24 mM), Meciadanol (0.24 mM), or sucralfate (0.35 mM) was significantly lower than those treated with nasogastric aspiration (0.87 mM) alone (P less than 0.01). This suggests that these substances bind bile salts and may provide additional protection to the gastric mucosa along with their ability to neutralize gastric acid.

Lack of clinically significant in vitro and in vivo interactions between ranitidine and sucralfate.

The hypothesis that the cytoprotective agent sucralfate (sucrose octakis(hydrogen sulfate)-aluminum complex) interacts with the H2-antagonist ranitidine (N-[2-[[dimethylamino)methyl]furfuryl]- thio]ethyl]-N'-methyl-2-nitro-1,1-ethenediamine) by decreasing ranitidine absorption was tested in vitro and in vivo. The in vitro results show that ranitidine may bind to a small extent (approximately 10%) to sucralfate paste in the gastrointestinal fluids. The in vivo ineraction of 150 mg of ranitidine and 1 g of sucralfate was evaluated in a crossover study in six healthy volunteers. The results indicate no significant difference in pharmacokinetic parameters when ranitidine was given alone and in combination with sucralfate. Thus, ranitidine bioavailability is not diminished by sucralfate and the two drugs can be given concomitantly. For the determination of bioavailability, it has to be taken into account that renal clearance of ranitidine is lower after oral than after intravenous administration, and that enterohepatic recirculation of the drug is likely.