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

Background: Helicobacter pylori plays an important role in the pathogenesis of peptic ulcer. Although several cytotoxins related to H. pylori have bee n reported, their effects on gastroduodenal mucosa have not been well evalu ated in vivo, Aim: To investigate the effects of the combination of acid and toxic substa nces derived from H. pylori on gastroduodenal mucosa, and to observe the ef fect 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 f orestomach for gastric luminal perfusion. In other animals, a cannula was i nserted to perfuse the proximal duodenum. Cr-51-EDTA was administered intra venously and mucosal integrity was monitored by measuring the blood-to-lume n Cr-51-EDTA clearance. After 72 h of culture of H. pylori (NCTC11637 and S ydney strain 1), Brucella broth containing 3% FBS was filtered to remove th e bacteria (supernate of H, pylori culture fluid; HPsup). HPsup was acidifi ed (pH = 2.0) with HCl, and tested for its injurious action on gastric or d uodenal mucosa by luminal perfusion, HPsup was incubated with sucralfate fo r 30 min, The supernate was collected by centrifugation and the pH was read justed 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 inj ury to the gastric mucosa. Non-acidified HPsup did not cause injury in the duodena mucosa, However, acidified HPsup induced a significantly greater in crease in Cr-51-EDTA clearance and greater histological damage than in cont rols. 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 a nti-ulcer action.