Enhancement of the protective qualities of gastric mucus by sucralfate: role of phosphoinositides

Article Abstract:

Sucralfate is a potent medication for the treatment of peptic ulcers. However, little is known about how sucralfate actually protects the stomach and promotes healing. This lack of knowledge is due in part to the fact the sucralfate has so many different effects on the stomach; it is not easy to determine which effects are most significant for the beneficial healing and protective actions. Most researchers believe, however, that a significant portion of sucralfate's benefits are physicochemical. That is to say, the benefits result from improvements in the physical and chemical barriers that normally protect the living cells lining the stomach and protecting it from the potent acids and enzymes within. In healthy tissues, this protection is provided by a lining of mucus. When patients with ulcers are treated with sucralfate, the sucralfate binds tenaciously to the ulcer itself, contributing to the protection of the injured areas. However, researchers have now found that sucralfate also changes the chemical composition of the mucus secreted by the stomach in ways that may make it more protective for the damaged tissues. In experimental ulcer studies performed on laboratory rats, it was found that the mucus secreted by the stomach was almost two times thicker (more viscous) after treatment with sucralfate. Results also revealed that, in the presence of sucralfate, the mucus manufactured by the stomachs was more hydrophobic and slowed the transit of hydrogen ions from the stomach acid. ('Hydrophobic' refers to the reluctance of substances to mix with water-based solutions, such as stomach acid.) In the course of documenting the increase in potentially protective characteristics of the stomach mucus, alterations in the phosphoinositide content of the stomach cells were found. Phosphoinositides are biochemical compounds consisting of related chemical modifications of the sugar-like substance inositol. Since cell biologists believe that these substances play an important role in the transmission of information within living cells, it is suspected that the observed changes in phosphoinositides represent a key step in the sequence of events leading to the alteration in mucus composition by the cells. (Consumer Summary produced by Reliance Medical Information, Inc.)

Phosphoinositides, Phosphatidylinositols, Gastric acid

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The effects of sucralfate and luminal stasis on recovery of the chambered rat gastric mucosa from taurocholate-induced damage

Article Abstract:

The compound sucralfate is well established in the treatment of peptic ulcers and related conditions. However, while there is no doubt that this treatment helps heal ulcers, there is actually little understanding of precisely how it works. One way of examining the function of sucralfate is by directly examining its effects on the stomachs of anesthetized laboratory rats. In a healthy stomach, a mucus layer coats the inside of the stomach. This mucus helps establish what physiologists call the pH gradient. That is, the contents of the stomach are highly acidic, or very low pH. The pH of the fluid rises, or becomes less acidic, as the mucus layer is crossed moving towards the living cells that actually line the stomach. The net result is that the living cells are in contact with fluid not nearly so acidic as much of the stomach's contents. The experimental treatment of the rat stomachs results in a decrease in the protective pH gradient of the mucus. However, the application of sucralfate restores the pH gradient to its normal levels; similar mechanisms may be at work in human ulcer patients. It has been suggested that the ability of sucralfate to promote prostaglandin synthesis leads to ulcer healing. The anti-inflammatory drug indomethacin inhibits the synthesis if prostaglandins. (Prostaglandins are biochemicals important in many body processes.) The chemical sodium taurocholate causes experimental ulcers in rats. In this study, it was found that pretreatment of the stomach with sucralfate decreased the size of the resulting ulcers. While treatment with indomethacin did not affect the ability of sucralfate to protect the stomach, it abolished the ability of sucralfate to speed the healing of the ulcers. This observation suggests that the physiological mechanisms by which sucralfate helps ulcers heal may be different from the mechanisms by which it helps prevent ulcers. (Consumer Summary produced by Reliance Medical Information, Inc.)

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Effects of sucralfate, lansoprazole, and cimetidine on the delayed healing by hydrocortisone sodium phosphate of chronic gastric ulcers in the rat

Article Abstract:

Patients chronically treated with steroid drugs appear to be at increased risk for developing peptic ulcers. Similarly, patients with a history of peptic ulcers appear to be at increased risk for recurrence of ulcers. The reason for this effect of steroids is not known. Hydrocortisone, a particular corticosteroid drug, impairs the healing of ulcers that have been experimentally induced in laboratory rats; a study was undertaken to compare several ulcer medications on the healing of stomach ulcers in such animals. The study compared cimetidine and sucralfate, both well established ulcer medications, as well as lansoprazole, a recently developed drug. The drugs were administered twice daily for two weeks, at which time the stomachs were examined and measured for signs of ulcer healing. The observations confirmed that hydrocortisone delayed the healing of the stomach ulcers. However, this delay was abolished by treatment with either lansoprazole or sucralfate. Treatment with the cimetidine had no effect on the slow healing of the experimentally induced ulcers in this animal model. (Consumer Summary produced by Reliance Medical Information, Inc.)

Complications and side effects, Risk factors, Corticosteroids, Adrenocortical hormones, Hydrocortisone, Cimetidine

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