Cell kinetics of mucosal atrophy in rat stomach induced by long-term administration of ammonia

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      Background: Helicobacter pylori produces ammonia in the stomach from urea. The present study was undertaken to clarify whether ammonia has an etiological role in H. pylori-associated gastric mucosal atrophy. Methods: Ammonia at 0.01% was administered as drinking water for 8 weeks and mucosal cell migration rate and cell proliferation were investigated in rat stomach. Results: Long-term administration of 0.01% ammonia for 4–8 weeks decreased mucosal thickness in the antrum but not in the body. Acceleration of cell migration preceded the occurrence of mucosal atrophy. Labeling indices in both antral and body mucosa significantly increased in all ammonia-treated groups, compared with those of the control group. In the antrum, the proliferative zone was significantly enlarged as mucosal atrophy developed, whereas, in body mucosa, enlargement of the proliferative zone occurred despite the absence of mucosal atrophy. Conclusion: Ammonia at 0.01% accelerates epithelial migration, especially in the antrum, leading to mucosal atrophy. Acceleration of epithelial proliferation occurs during the development of mucosal atrophy.


      BrdU (5-bromo-2′deoxyuridine), HP (Hellcobactor pylori), LI (labeling Index), PZ (proliferative index), TCA (taurocholic acid)
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        • Warren JR
        • Marshall BJ
        Unidentified curved bacilli on gastric epithelium in acute chronic gastritis.
        Lancet. 1983; 1: 1273-1275
        • Marshall BJ
        • Warren JB
        Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration.
        Lancet. 1984; 6: 1311-1314
        • Buck GE
        • Gourley WK
        • Lee WK
        • Surramanyan K
        • Latimer JM
        • Di-Nuzzo AR
        Relation of Campylobacter pyloridis to gastritis and peptic ulcer.
        J Infect Dis. 1986; 153: 664-669
        • Dixon MF
        • Wyatt JI
        • Burke DA
        • Rathobone BJ
        Lymphocytic gastritis-relationship to Campylobacter pylori infection.
        J Pathol. 1988; 154: 125-132
        • Kekki M
        • Varis K
        • Pohjanpalo H
        • Isokoski M
        • Ihamaki T
        • Siurala M
        Course of antrum and body gastritis in pernicious anemia families.
        Dig Dis Sci. 1983; 28: 698-704
        • Karnes WE
        • Samloff IM
        • Siurala M
        • Kekki M
        • Sipponen P
        • Kim WR
        • Walsh JH
        Positive serum antibody and negative tissue staining for Helicobacter pylori in subjects with atrophie body gastritis.
        Gastroenterology. 1991; 101: 167-174
        • Kochiyama T
        Clinical study of Campylobater pylori in stomach disease.
        Gastroenterol Endosc. 1989; 31: 3-13
        • Mobley HL
        • Hu LT
        • Foxal PA
        Helicobacter pylori urease: properties and role in pathogenesis.
        Scand J Gastroenterol. 1991; 187: 39-46
        • Tsujii M
        • Kawano S
        • Tsuji S
        • Fusamoto H
        • Kamada T
        • Sato N
        Mechanism of gastric mucosal damage induced by ammonia—Impairment of energy metabolism due to ammonia.
        Gastroenterology. 1992; 102: 1881-1888
        • Kawano S
        • Tsujii M
        • Fusamoto H
        • Sato N
        • Kamada T
        Chronic effect of intragastric ammonia on gastric mucosal structures in rats.
        Dig Dis Sci. 1991; 36: 33-38
        • Assad RT
        • Eastwood GL
        Epithelial proliferation in human fundic mucosa after antrectomy and vagotomy.
        Gastroenterol. 1980; 79: 807-811
        • Shay H
        • Sun DCH
        • Gruenstein M
        A quantitative method for measuring spontaneous gastric secretion in the rat.
        Gastroenterol. 1954; 26: 906-913
        • Glass GB
        • Pitchumoni CS
        Atrophic gastritis. Structural and ultrastructural alterations, exfoliative cytology and enzyme cytochemistry and histochemistry, proliferation kinetics, immunological derangements and other causes, and clinical associations and sequellae.
        Hum Pathol. 1975; 6: 219-250
        • Deshner EE
        • Winawer SJ
        • Lipkin M
        Patterns of nucleic acid and protein synthesis in normal human gastric mucosa and atrophic gastritis.
        JNCI. 1972; 48: 1567-1574
        • Deschner EE
        • Tamura K
        • Bralow SP
        Early proliferative changes in rat pyloric mucosa induced by N-methyl-N′-nitro-N-nitrosoguanidine.
        Front Gastrointest Res. 1984; 4: 25-31
        • Lipkin M
        Phase 1 and phase 2 proliferative lesions of colonic epithelial cells in diseases leading to colonic cancer.
        Cancer. 1974; 34: 878-888
        • Kishimoto S
        • Ogawa M
        • Takaba N
        • Konemori R
        • Kambara A
        • Okamaoto K
        • Shimizu S
        • Yamamoto M
        • Kajiyama G
        Curative effect of gastripylore on taurocholate-induced gastritis in rats.
        Japan Arch Intern Med. 1985; 32: 297-302
        • May RJ
        • Quaroni A
        • Kirsch K
        • Isselbacher KJ
        A villous cell-derived inhibitor of intestinal cell proliferation.
        Am J Physiol. 1981; 241: G520-G527
        • Willems G
        Cellular kinetics and gastric mucosdal disease.
        in: Magen und Magenkrankheiten. Thieme, Stuttgart, Germany1981: 195-204
        • Townsley MC
        • Paradiso AM
        • Machen TE
        Na/H exchange in antral cells isolated from Necturus, rabbit, and guinea pig.
        Gastroenterology. 1988; 95: 302-310
        • Busa W
        • Nuccitelli R
        Metabolic regulation via intracellular pH.
        Am J Physiol. 1984; 246: R409-R438
        • Ito T
        • Hayashi N
        • Sasaki Y
        • Morita Y
        • Kawano S
        • Fusamoto H
        • Sato N
        • Tohyama M
        • Kamada T
        Sequential protooncogene expression during regeneration in rat stomach.
        Gastroenterology. 1990; 98: 1525-1531
        • Townsend SF
        Regeneration of gastric mucosa in rats.
        Am J Anat. 1961; 109: 133-141
        • Finckh ES
        • Milton GW
        Regeneration of gastric mucosa from differentiated cells.
        J Pathol Bacteriol. 1960; 80: 143-145
        • Hunt TE
        • Hunt EA
        Radioautographic study of proliferation in the stomach of the rat using thymidine-H3 and compound 48/80.
        Anat Rec. 1962; 142: 505-511
        • Hattori T
        • Helpap B
        • Gedigk P
        The morphology and cell kinetics of pseudopyloric glands.
        Virc Arc B. 1982; 39: 31-40
        • Johnson LR
        Regulation of gastrointestinal growth.
        in: Johnson LR Physiology of the gastrointestinal tract. Raven, New York1981: 169-196
        • Deshner EE
        • Winawer SJ
        • Lipkin M
        Patterns of nucleic acid and protein synthesis in normal human gastric mucosa and atrophic gastritis.
        JNCI. 1972; 48: 1567-1574
        • Thomsen LL
        • Gavin JB
        • Tasman-Jones C
        Relation of Helicobacter pylori to the human gastric mucosa in chronic gastritis of the antrum.
        Gut. 1990; 31: 1230-1236