Bismuth subsalicylate was tested in an in vivo perfused rabbit model of oesophagitis for its ability to prevent the mucosal injury caused by pepsin. Treatment efficacy was assessed under both a treatment-before-injury protocol and a treatment-after-injury protocol. Oesophageal mucosal barrier function was evaluated by measuring flux rates of H+, K+, and glucose. The degree of oesophagitis was determined by gross and microscopic examination of the mucosa by several independent observers. Results showed that under both treatment protocols, bismuth subsalicylate significantly reduced the pepsin induced disruption of the mucosal barrier, as well as the morphologic changes. Bismuth subsalicylate when given after exposure to pepsin was also found to protect against the morphologic injury in a dose dependent manner. Experiments in vitro suggested that bismuth subsalicylate inhibits the proteolytic action of pepsin by interacting with pepsin, rather than with the pepsin substrate. We conclude that bismuth subsalicylate can protect the oesophageal mucosa against peptic injury, probably through inactivation of pepsin.
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