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Nonsteroidal anti-inflammatory drugs (NSAIDs) contribute to the esophageal mucosal injury through its direct topical impact on the luminal aspect of the surface epithelium. Its indirect, systemic impact, however, on salivary component of the esophageal pre-epithelial barrier remains to be explored. Therefore, salivary mucin secretion and viscosity at baseline and during naproxen-placebo, as well as naproxen-rabeprazole, administration were investigated.Twenty-one asymptomatic volunteers were included in this double-blind, placebo-controlled, crossover designed study. Salivary samples were obtained in basal and pentagastrin-stimulated conditions (6 mg/kg s.c.) mimicking the food-stimulated conditions. Patients received 7 days of naproxen-placebo or naproxen-rabeprazole with a 2-week washout period in between. Salivary mucin content and viscosity were measured before and after treatment using periodic acid/Schiff's methodology and Cone/Plate Digital Viscometer, respectively.The rate of salivary mucin secretion in basal condition declined by 32% during administration of naproxen-placebo (11.3±1.7 vs. 16.8±3.3 mg/h). Salivary mucin secretion in pentagastrin-stimulated condition declined significantly (by 34%) during the administration of naproxen-placebo (13.6±1.5 vs. 20.7±3.0 mg/h; P<0.05). Viscosity significantly decreased after naproxen-placebo administration in basal (by 60%) and stimulated conditions (by 56%) (P<0.001). Coadministration of rabeprazole at least partly restored the naproxen-induced decline of salivary mucin in basal condition (by 8%), and pentagastrin-stimulated conditions (by 30%).A significant decline of salivary mucin and viscosity during administration of naproxen may at least partly explain a propensity of patients on chronic therapy with NSAIDs to the development of esophageal mucosal injury and complications. In addition the trend to restorative capacity of rabeprazole on the quantitative impairment of salivary mucin during administration of naproxen may potentially translate into its tangible clinical benefit but it requires further investigation.

clinical and translational gastroenterology

Impairment of Salivary Mucin Production Resulting in Declined Salivary Viscosity During Naproxen Administration as a Potential Link to Upper Alimentary Tract Mucosal Injury