Injurious effect of Helicobacter pylori culture fluid to gastroduodenal mucosa, and its detoxification by sucralfate in the rat

Abstract

Background: Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer. Although several cytotoxins related to H. pylori have been reported, their effects on gastroduodenal mucosa have not been well evaluated in vivo. Aim: To investigate the effects of the combination of acid and toxic substances derived from H. pylori on gastroduodenal mucosa, and to observe the effect of sucralfate on such factors in the rat. Methods: Male Sprague-Dawley rats were fasted overnight and anaesthetized. The pylorus was ligated, and a double-lumen cannula was inserted into the forestomach for gastric luminal perfusion. In other animals, a cannula was inserted to perfuse the proximal duodenum, 51Cr-EDTA was administered intravenously and mucosal integrity was monitored by measuring the blood-to-lumen 51Cr-EDTA clearance. After 72 h of culture of H. pylori (NCTC11637 and Sydney strain 1), Brucella broth containing 3% FBS was filtered to remove the bacteria (supernate of H. pylori culture fluid: HPsup). HPsup was acidified (pH = 2.0) with HC1, and tested for its injurious action on gastric or duodenal mucosa by luminal perfusion. HPsup was incubated with sucralfate for 30 min. The supernate was collected by centrifugation and the pH was readjusted to 2.0. This sucralfate-treated HPsup was used to test the effect of sucralfate against H. pylori-related mucosal injurious factors. Results: Non-acidified and acidified HPsup did not cause any detectable injury to the gastric mucosa. Non-acidified HPsup did not cause injury in the duodenal mucosa. However, acidified HPsup induced a significantly greater increase in 51Cr-EDTA clearance and greater histological damage than in controls. Sucralfate completely reversed this. Conclusion: These results suggest that an H. pylori-related toxic substance may aggravate duodenal acid injury by acting on luminal surfaces, and that the detoxification of this substance by sucralfate may contribute to its anti-ulcer action.