Abstract
We have previously suggested (Trevethick et al., Gut34, 156–160) that indomethacin-induced ulceration of the rat gastric antrum may be a neutrophil-dependent process. Accordingly, in this study we have used an anti-neutrophil serum (ANS) to investigate the effects of neutrophil depletion on this pathology. In animals pretreated with the ANS to induce a nearly total neutropaenia, indomethacin-induced increases in blood neutrophilia and cell infiltration into the gastric antrum (assessed as LTB4 releaseex vivo) were eliminated. In marked contrast, however, ANS pretreatment affected neither the area of mucosa damaged nor the microscopic characteristics or distribution of the lesions. These results suggest that, in contrast to the published reports examining indomethacin-induced ulceration of the gastric fundus, neutrophil infiltration is not involved in the pathogenesis of indomethacin-induced ulceration of the rat gastric antrum.
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References
J. F. Fries, C. A. Williams and D. A. Bloch,The relative toxicity of non-steroidal anti-inflammatory drugs. Arth. Rheum.34, 1353–1360 (1991).
J. L. Wallace, C. M. Keenan and D. N. Granger,Gastric ulceration induced by non-steroidal anti-inflammatory drugs is a neutrophil dependent process. Am. J. Physiol.259, G462-G467 (1990).
J. L. Wallace, K. E. Arfors and G. W. McKnight,A monoclonal antibody against the CD18 leucocyte adhesion molecule prevents indomethacin-induced gastric damage in the rabbit. Gastroenterology100, 878–883 (1991).
M. Lee, K. Aldred, E. Lee and M. Feldman,Aspirin-induced acute gastric mucosal injury is a neutrophil-dependent process in rats. Am. J. Physiol.263, G920-G926 (1992).
S. H. Roth and R. E. Bennet,Non-steroidal anti-inflammatory drug gastropathy: Recognition and response. Arch. Int. Med.147, 2093–3100 (1987).
K.-P. Stock and G. L. Bach,Ulcer healing with ranitidine and antacids despite continued treatment with non-steroidal anti-inflammatory drugs. Z. Rheumatol.47, 177–181 (1988).
M. A. Trevethick, N. M. Clayton, P. Strong and I. W. HarmanDo infiltrating neutrophils contribute to the pathogenesis of indomethacin-induced ulceration of the rat gastric antrum. Gut34, 156–160 (1993).
M. A. Trevethick, N. M. Clayton, A. K. Bahl, S. Sanjar and P. Strong,Neutrophil depletion does not prevent indomethacin-induced ulceration of the rat gastric antrum. Agents and Actions41, C226-C227 (1994).
J. L. Wallace and D. N. Granger,Pathogenesis of NSAID-gastrophy: Are neutrophils the culprits? TiPS13, 129–131 (1992).
M. A. Trevethick, N. M. Clayton, A. K. Bahl, P. Strong and I. W. Harman,Leukotrienes do not contribute to the pathogenesis of indomethacin-induced ulceration of the rat gastric antrum in the re-fed rat. Agents and Actions41, 179–183 (1994).
B. M. Peskar, K. Larnge, W. Hoppa and B. A. Peskar,Ethanol stimulates formation of leukotriene C4 in rat gastric mucosa. Prostaglandins31, 283–294 (1986).
S. J. Galli, B. K. Wershil, R. Bose, P. A. Walker and S. Szabo,Ethanol-induced acute gastric injury in mast cell deficient and congenic normal mice. Am. J. Pathol.128, 131–140 (1987).
F. Karmel, R. Eliakim, E. Okan and D. rachmielwitz,Gastric mucosal damage by ethanol is mediated by substance P and prevented by ketotifen, a mast cell stabiliser. Gastroenterology100, 1206–1216 (1991).
R. Eliakim, F. Karmel and D. Rachmilewitz,Ketotifen—old drug, new indication: Reduction of gastric mucosal injury. Scand. J. Gatroenterol.28, 202–204 (1993).
K. Soda, S. Kawabori, M. H. Perdua and J. Bienstock,Macrophage engulfment of mucosal mast cells in rats treated with dexamethasone. Gastroenterology100, 929–937 (1991).
P. Goldsmith, B. McGarity, A. F. Walls, M. K. Church, G. H. Millward-Sadler and D. A. F. Robertson,Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. Dig. Dis. Sci.35, 1409–1413 (1990).
S. Moncada and A. Higgs, Thel-arginine-nitric oxide pathway. N. Engl. J. Med.329, 2002–2012 (1993).
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Trevethick, M.A., Bahl, A.K., Clayton, N.M. et al. Neutrophil infiltration does not contribute to the ulcerogenic effects of indomethacin in the rat gastric antrum. Agents and Actions 43, 39–43 (1994). https://doi.org/10.1007/BF02005762
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DOI: https://doi.org/10.1007/BF02005762