Sulphasalazine and PhCL28A inhibit the formation of ethanol‐ and phenylbutazone‐induced rat gastric ulcers: lack of involvement of endogenous prostaglandins?

• Published in: British journal of pharmacology Vol. 93; no. 3; pp. 465 - 472
• Main Authors: Berry, C.N., Prouteau, M., Lloyd, K.G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.1988; Nature Publishing
• Subjects: Animals; Azo Compounds - pharmacology; Biological and medical sciences; Digestive system; Ethanol; Female; Medical sciences; Pharmacology. Drug treatments; Phenylbutazone; Prostaglandins - metabolism; Prostaglandins - physiology; Rats; Rats, Inbred Strains; Stomach Ulcer - chemically induced; Stomach Ulcer - prevention & control; Sulfasalazine - pharmacology; Stomach; Intraperitoneal administration; Ethanol; Rat; Arachidonic acid derivatives; Rodentia; Antiulcer agent; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Animal; Digestive diseases; Ulcer; Mechanism of action; Gastric disease
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1988.tb10300.x

1 The effects of sulphasalazine (SZP) and PhCL28A on macroscopic lesion formation and ex vivo prostaglandin inactivation were studied in the ethanol (ETOH) and phenylbutazone (PBT) models of gastric ulcers in the rat. Prostaglandin ‘synthesis’ during homogenisation of the stomachs was also studied in the latter model. 2 Both PhCL28A and SZP when injected i.p. prevented the formation of ETOH‐ and PBT‐induced gastric ulcers with ED50 values of 13 and 41 mg kg−1 (vs ETOH) and 3 and 32 mg kg−1 (vs PBT) for PhCL28A and SZP respectively. However, neither compound was active orally in the dose ranges used (up to 30 mg kg−1 for PhCL28A and 100 mg kg−1 for SZP). 3 Irrespective of the route of administration, SZP (100 mg kg−1) and PhCL28A (30 mg kg−1) produced slight but statistically significant decreases in ex vivo prostaglandin inactivation by 100,000 g cytosolic supernatants prepared from stomachs not receiving ulcerogen. When tested in vitro, PhCL28A (IC50 = 230 nM) was approximatively 480 times more potent than SZP (IC50 = 110 μM) against rat stomach cytosolic prostaglandin inactivation. 4 Both ETOH (50%, 5 ml kg‐1, orally) and PBT (200 mg kg−1 orally) significantly decreased ex vivo gastric cytosolic prostaglandin inactivation. PhCL28A (30 mg kg−1, orally or i.p.) decreased prostaglandin inactivation still further after ulcerogen treatment except when given i.p. before ETOH treatment. SZP (100 mg kg−1) had a similar effect when given orally before PBT treatment. 5 When the prostaglandin content of the stomach homogenates was used as a measure of ex vivo prostaglandin synthesis in the PBT experiments, PhCL28A 30 mg kg−1 orally (but not i.p.) produced an 88% increase in prostaglandin E2 (PGE2) levels, but had no effect on 6‐keto‐PGF1α or thromboxane B2 formation during homogenization. SZP (100 mg kg−1 i.p. or orally) was without effect. 6 We conclude from these results that the anti gastric ulcer activity of SZP and PhCL28A is independent of prostaglandin inactivation and endogenous prostaglandin formation is probably not involved.