title: Restorative impact of rabeprazole on gastric mucus and mucin production impairment during naproxen administration: its potential clinical significance.
abstract: 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 CsC1. 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.
authors.affiliation: Kansas University Medical Center, Division of Gastroenterology and Hepatology, Center for Muscle and Nerve Function, Gastroenterology Research Laboratory, Kansas City, Kansas 66160-7350, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jaworski
authors.forename: I
authors.initials: I
authors.lastname: Sarosiek
authors.forename: S
authors.initials: S
authors.lastname: Sostarich
authors.forename: K
authors.initials: K
authors.lastname: Roeser
authors.forename: M
authors.initials: M
authors.lastname: Connor
authors.forename: S
authors.initials: S
authors.lastname: Brotze
authors.forename: G
authors.initials: G
authors.lastname: Wallner
authors.forename: J
authors.initials: J
authors.lastname: Sarosiek
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005088:Exocrine Glands / Q000187:drug effects; D005260:Female; D005750:Gastric Juice / Q000737:chemistry*; D005752:Gastric Mucins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009093:Mucus / Q000378:metabolism*; D009288:Naproxen / Q000494:pharmacology* / Q000627:therapeutic use; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D064750:Rabeprazole
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D005752:Gastric Mucins; D064750:Rabeprazole; D009288:Naproxen; D006180:Proton-Translocating ATPases; D009853:Omeprazole
references.citation: Scand J Gastroenterol Suppl. 1989;160:53-8
references.pmid: 2683023
references.citation: Am J Gastroenterol. 1993 Sep;88(9):1362-5
references.pmid: 8362831
references.citation: Am J Gastroenterol. 1996 Feb;91(2):360-5
references.pmid: 8607507
references.citation: Am J Physiol. 1983 May;244(5):G561-8
references.pmid: 6846549
references.citation: Gastroenterology. 1979 Oct;77(4 Pt 1):719-29
references.pmid: 467928
references.citation: Gut. 1980 Jun;21(6):533-6
references.pmid: 7429315
references.citation: Biochem Biophys Res Commun. 1988 Mar 30;151(3):1046-53
references.pmid: 3281667
references.citation: Dig Dis. 1987;5(3):125-45
references.pmid: 3311486
references.citation: Am J Med Sci. 1991 Dec;302(6):359-63
references.pmid: 1772120
references.citation: Pharmacotherapy. 1997 Jan-Feb;17(1):22-37
references.pmid: 9017763
references.citation: Annu Rev Pharmacol Toxicol. 1998;38:97-120
references.pmid: 9597150
references.citation: Gastroenterology. 1994 Apr;106(4):973-81
references.pmid: 8144002
references.citation: Gastroenterology. 1987 Jun;92(6):1876-84
references.pmid: 3569763
references.citation: Physiol Rev. 1993 Oct;73(4):823-57
references.pmid: 8415927
references.citation: Am J Gastroenterol. 1995 Nov;90(11):2020-4
references.pmid: 7485014
references.citation: Biochem Biophys Res Commun. 1983 Sep 30;115(3):1053-60
references.pmid: 6414477
references.citation: Scand J Gastroenterol. 1988 Jun;23(5):585-90
references.pmid: 3399831
references.citation: Scand J Gastroenterol Suppl. 1991;187:47-55
references.pmid: 1775924
references.citation: Gastroenterology. 1999 Oct;117(4):776-83
references.pmid: 10500058
references.citation: Am J Gastroenterol. 1991 Jun;86(6):729-34
references.pmid: 2038995
references.citation: Am J Gastroenterol. 1993 Dec;88(12):2038-43
references.pmid: 8249971
references.citation: Am J Gastroenterol. 1992 Oct;87(10):1398-402
references.pmid: 1415094
references.citation: Drug Saf. 1996 Oct;15(4):249-60
references.pmid: 8905250
references.citation: Annu Rev Pharmacol Toxicol. 1995;35:277-305
references.pmid: 7598495
references.citation: Biochem Pharmacol. 1987 Dec 1;36(23 ):4059-65
references.pmid: 2446628
references.citation: Dig Dis Sci. 1994 Dec;39(12):2523-9
references.pmid: 7995174
references.citation: N Engl J Med. 2000 Nov 23;343 (21):1520-8, 2 p following 1528
references.pmid: 11087881
references.citation: Scand J Gastroenterol Suppl. 1993;196:12-6
references.pmid: 8341986
references.citation: Am J Gastroenterol. 1996 May;91(5):873-8
references.pmid: 8633574
references.citation: Biochem Pharmacol. 1986 Dec 1;35(23):4291-5
references.pmid: 3098249
references.citation: Biochem Biophys Res Commun. 1984 Jan 30;118(2):523-31
references.pmid: 6704093
references.citation: Dig Dis Sci. 2003 Feb;48(2):322-8
references.pmid: 12643610