Abstract
The effects of sulphasalazine on gastric ulceration induced by restraint at 4°C (stress) for 2 h were studied in rats. Doses of 63 or 125 mg/kg s.c., which had no effect on stomach wall prostaglandin E2 (PGE2) levels, prevented stress ulceration but not the lesions produced by indomethacin. Stress significantly increased gastric glandular mucosal PGE2 levels. Indomethacin pretreatment (20 mg/kg, p.o.) markedly reduced PGE2 levels in the same region of the stomachs, and worsened stress-induced lesion formation. Pretreatment with sulphasalazine of animals given indomethacin and then subjected to stress did not appear to affect the indomethacin component of indomethacin-stress ulceration. Oral administration of PGE2 200 μg/kg significantly elevated gastric PGE2 levels, but had no effect on stress ulceration.
It appears that neither the antiulcer activity of sulphasalazine nor stress-induced ulceration is associated with gastric tissue PGE2 increase or decrease, respectively. The protective mechanism may result from the ability of sulphasalazine to inhibit lipoxygenase activity.
Similar content being viewed by others
References
N. Svartz,Salazopyrin, a new sulfanilamide preparation, Acta Med. Scand.110, 577–598 (1942).
S. R. Gould,Prostaglandins, ulcerative colitis, and sulphasalazine, LancetII, 988 (1975).
J. C. Sircar, C.F. Schwender andM.E. Carethers,Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis, Biochem. Pharmac.32, 170–172 (1983).
A. Foca, G. Matera, D. Altavilla, P. Mastroeni andA.P. Caputi,Sulphasalazine reduces endotoxin lethality in the rat, IRCS Med. Sci.11, 865–866 (1983).
M.E. Goldyne, Prostaglandins & other eicosanoids. InBasic & Clinical Pharmacology, pp. 217–226 (Ed.B.G. Katzung). Lange, Los Altos 1984.
C. H. Cho andC.W. Ogle,Histamine H 1-and H 2-receptor-mediated gastric microcirculatory effects in the aetiology of stress ulceration in the rat stomach, Experientia34, 1294–1295 (1978).
C.H. Cho andC.W. Ogle,Cholinergic-mediated gastric mast cell degranulation with subsequent histamine H 1-and H 2-receptor activation in stress ulceration in rats, Eur. J. Pharmac.55, 23–33 (1979).
J.R.S. Hoult andP.K. Moore,Effects of sulphasalazine and its metabolites on prostaglandin synthesis, inactivation and actions on smooth muscle, Br. J. Pharmac.68, 719–730 (1980).
G.P. Morris, J.L. Wallace andP.L. Harding,Effects of prostaglandin E 2 on salicylate-induced damage to the rat gastric mucosa: cytoprotection is not associated with preservation of the gastric mucosal barrier, Can. J. Physiol. Pharmac.62, 1065–1069 (1983).
A. Robert, J.E. Nezamis, C. Lancaster andA.J. Hanchar,Cytoprotection of prostaglandin in rats: Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl and thermal injury, Gastroenterology77, 433–443 (1979).
S.J. Konturek, I. Piastucjki, T. Brzozowski, T. Radecki, A. Dembinska-Kiec, A. Zmuda andR. Gryglewski,Role of prostaglandins in the formation of aspirin-induced gastric ulcers, Gastroenterology80, 4–9 (1981).
O.H. Lowry, N.J. Rosebrough, A.L. Farr andR.J. Randall,Protein measurement with the folin phenol reagent, J. Biol. Chem.193, 265–275 (1951).
P.J. Piper,Formation and actions of leukotrienes, Physiol. Rev.64, 744–761 (1984).
P.J. Piper, M.N. Samhoun, J.R. Tippins, T.J. Williams, M.A. Palmer andM.J. Peck,Pharmacological studies on pure SRS-A, and synthetic leukotrienes C 4 and D 4. InSRS-A and Leukotrienes, pp. 81–99 (Ed.P.J. Piper). Wiley, New York 1981.
M.J. Peck, P.J. Piper andT.J. Williams,The effects of leukotrienes C 4 and D 4 on the microvasculature of guinea-pig skin, Prostaglandins21, 315–321 (1981).
C.H. Cho, C.J. Pfeiffer andA. Cheema,Studies of zinc and histamine on lysosomal fragility: possible role in stress ulceration, Pharmac. Biochem. Behav.13, 41–44 (1980).
S. Dai andC.W. Ogle,Gastric ulcers induced by acid accumulation and by stress in pylorus-occluded rats, Eur. J. Pharmac.26, 15–21 (1974).
K.E. Barrett, T.L. Tashof andD.D. Metcalfe,Inhibition of IgE-mediated mast cell degranulation by sulphasalazine, Eur. J. Pharmac.107, 279–281 (1985).
C.W. Ogle andC.H. Cho,Effects of sulphasalazine on stress ulceration and mast cell degranulation in rat stomachs, Eur. J. Pharmac.112, 285–286 (1985).
C.W. Ogle andH.K. Lau,Disodium cromoglycate: a novel gastric antiulcer agent?, Eur. J. Pharmac.55, 411–415.
G.L. Mandell andM.A. Sande, Antimicrobial agents. InThe Pharmacological Basis of Therapeutics, pp. 1106–1125 (Eds.A.G. Gilman, L.S. Goodman andA. Gillman). Macmillan, New York 1980.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ogle, C.W., Cho, C.H. & Dai, S. Sulphasalazine and experimental stress ulcers. Agents and Actions 17, 153–157 (1985). https://doi.org/10.1007/BF01966585
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01966585