Rabeprazole augments gastric mucus and mucin production in humans. However, its potential restorative impact on gastric mucus and mucin production impairment, resulting from administration of naproxen, remained to be explored. Therefore, we measured the content of mucus and mucin in gastric juice (GJ) before and after administration of naproxen with rabeprazole or placebo. The study was approved by HSC at KUMC and conducted in 21 asymptomatic, H. pylori–negative volunteers in a double-blind, placebo-controlled, crossover design. The content of gastric mucus in GJ, after exhaustive dialysis and complete lyophilization, was assessed gravimetrically, whereas the content of mucin was measured after its purification with equilibrium density-gradient ultracentrifugation in CsCl. Gastric mucus secretion during administration of naproxen with placebo declined significantly both in basal (by 44%; P < 0.001) and in pentagastrin-stimulated (by 35%; P < 0.001) conditions. Coadministration of rabeprazole significantly restored the naproxen-induced impairment in mucus production in basal conditions (by 47%; P < 0.01) and by 22% during stimulation with pentagastrin. Gastric mucin secretion during naproxen/placebo administration also declined significantly in both basal (by 39%; P < 0.01) and stimulated (by 49%; P = 0.003) conditions. Rabeprazole also significantly restored the naproxen-induced decline of gastric mucin output during pentagastrin-stimulated conditions (by 67%; P = 0.003) and by 40% in basal conditions (P = 0.05). The restorative capacity of rabeprazole on the quantitative impairment of gastric mucus and mucin during administration of naproxen may translate into a clinical benefit of protection of the upper alimentary tract from NSAID-related mucosal injury.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bombardier C, Laine L, Reicin A, et al.: Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 343:1520–1528, 2000
Laine L, Marin-Sorensen M, Weinstein WM: Nonsteroidal antiinflammatory drug-associated gastric ulcers do not require Helicobacter pylori for their development. Am J Gastroenterol 87:1398–1402, 1992
Sarosiek J, Marcinkiewicz M, Parolisi S, et al.: The content of prostaglandin E2 in residual gastric juice reflects endoscopic damage to the gastric mucosa after naproxen sodium administration. Am J Gastroenterol 91:873–878, 1996
Marcinkiewicz M, Sarosiek J, Peura DA: The relationship between the content of gastric mucus protective components in gastric juice and endoscopic damage to the gastric mucosa after naproxen sodium administration. Am J Gastroenterol 91:360–365, 1996
Sarosiek J, Marshall BJ, Peura DA, et al.: Gastroduodenal mucus gel thickness in patients with Helicobacter pylori: A method for assessment of biopsy specimens. Am J Gastroenterol 86:729–734, 1991
Slomiany BL, Sarosiek J, Slomiany A: Gastric mucus and the mucosal barrier. Dig Dis 5:125–145, 1987
Allen A: Structure and function of gastrointestinal mucus. In: Johnson LR (ed). Physiology of the Gastrointestinal Tract. New York, Raven Press, 1981, pp. 617–639
Allen A, Flemstrom G, Garner A, et al.: Gastroduodenal mucosal protection. Physiol Rev 73:823–857, 1993
Peterson WL, Barnett CC, Evans DJJr, et al.: Acid secretion and serum gastrin in normal subjects and patients with duodenal ulcer: the role of Helicobacter pylori [see comments]. Am J Gastroenterol 88:2038–2043, 1993
Hunt RH: Hp and pH: Implications for the eradication of Helicobacter pylori. Scand J Gastroenterol Suppl 19:12-6–12–16, 1993
Wormsley KG: Campylobacter pylori and ulcer disease—A causal connection. Scand J Gastroenterol Suppl 160:53–58, 1989
Sarosiek J, Mizuta K, Slomiany A, et al.: Effect of acetylsalicylic acid on gastric mucin viscosity, permeability to hydrogen ion and susceptibility to pepsin. Biochem Pharmacol 35:4291–4295, 1986
Sarosiek J, Slomiany A, Slomiany BL: Retardation of hydrogen ion diffusion by gastric mucus constituents: Effect of proteolysis. Biochem Biophys Res Commun 113:1053–1060, 1983
Sarosiek J, Slomiany A, Slomiany BL: Evidence for weakening of gastric mucus integrity by Campylobacter pylori. Scand J Gastroenterol 23:585–590, 1988
Sarosiek J, Feng T, McCallum RW: The interrelationship between salivary epidermal growth factor and the functional integrity of the esophageal mucosal barrier in the rat. Am J Med Sci 302:359–363, 1991
Bilski J, Sarosiek J, Murty VLN, et al.: Enhancament of the lipid content and physical properties of gastric mucus by geranylgeranylacetone. Biochem Pharmacol 36:4059–4065, 1987
Azuumi Y, Ohara S, Ishihara K, et al.: Correlation of quantitative changes of gastric mucosal glycoproteins with aspirin-induced gastric damage in rats. Gut 21:533–536, 1980
Sachs G, Shin JM, Briving C, et al.: The pharmacology of the gastric acid pump: The H+,K+ ATPase. Annu Rev Pharmacol Toxicol 35:277–305, 1995
Takiuchi H, Asada S, Umegaki E, et al.: Effects of proton pump inhibitors: omeprazole, lansoprazole, and E-3810 on the gastric mucin. 1404P, 1994 (abstract)
Skoczylas T, Sarosiek I, Sostarich S, et al.: Significant enhancement of gastric mucin content after rabeprazole administration: Its potential clinical significance in acid-related disorders. Dig Dis Sci 48:322–328, 2003
Namiot Z, Sarosiek J, Rourk RM, et al.: Human esophageal secretion: Mucosal response to luminal acid and pepsin. Gastroenterology 106:973–981, 1994
Richardson C, Emery P: The clinical implications of inhibition of the inducible form of cyclo-oxygenase. Drug Saf 15:249–260, 1996
Vane JR, Bakhle YS, Botting RM: Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol 38:97–120, 1998
Laine L, Harper S, Simon T, et al.: A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteorthritis. Gastroenterology 117:776–783, 1999
Sachs G: Proton pump inhibitors and acid-related diseases. Pharmacotherapy 17:22–37, 1997
Zalewsky CA, Moody FG: Mechanisms of mucus release in exposed canine gastric mucosa. Gastroenterology 79:719–730, 1979
Sarosiek J, Slomiany A, Takagi T, et al.: Hydrogen ion diffusion in dog gastric mucus glycoprotein: Effect of associated lipids and covalently bound fatty acids. Biochem Biophys Res Commun 118:523–531, 1984
Quigley EMM, Turnberg LA: pH of the microclimate lining human gastric and duodenal mucosa in vivo: Studies in control subjects and in duodenal ulcer patients. Gastroenterology 92:1976–1984, 1987
Namiot Z, Sarosiek J, Marcinkiewicz M, et al.: Declined human esophageal mucin secretion in patients with severe reflux esophagitis. Dig Dis Sci 39:2523–2529, 1994
Slomiany BL, Murty VLN, Sarosiek J, et al.: Role of associated and covalently bound lipids in salivary mucin hydrophobicity: Effect of proteolysis and disulphide bridge reduction. Biochem Biophys Res Commun 151:1046–1053, 1988
Hills BA, Butler BD, Lichtenberger LM: Gastric mucosal barrier: Hydrophobic lining to the lumen of the stomach. Am J Physiol 244:G561–G568, 1983
Go MF, Lew GM, Lichtenberger LM, et al.: Gastric mucosal hydrophobicity and Helicobacter pylori: Response to antimicrobial therapy. Am J Gastroenterol 88:1362–1365, 1993
DeRosa J, Marcinkiewicz M, Sarosiek J, et al.: Modulatory impact of acid and pepsin on esophageal hydrophobicity in human. Am J Gastroenterol 90:2020–2024, 1995
Sarosiek J, Peura D, Guerrant RL, et al.: Mucolytic effects of Helicobacter pylori. Sc J Gastroenterol 1991;26, Suppl. 187:47–55.
Sarosiek J, Namiot Z, Marshall BJ, et al.: Breakdown of the mucus layer by H. pylori. In: Hunt RH, Tytgat GNJ, eds. Helicobacter pylori: Basic mechanisms to clinical cure. Kluwer Academic Publishers: Dordrecht/Boston/London, 1994:123–138
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Jaworski, T., Sarosiek, I., Sostarich, S. et al. Restorative Impact of Rabeprazole on Gastric Mucus and Mucin Production Impairment During Naproxen Administration: Its Potential Clinical Significance. Dig Dis Sci 50, 357–365 (2005). https://doi.org/10.1007/s10620-005-1611-3
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10620-005-1611-3