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

Abstract

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 ED,5 values of 13 and 41 mg kg-' (vs ETOH) and 3 and 32 mg kg-' (vs PBT) for PhCL28A and SZP respectively. However, neither compound was active orally in the dose ranges used (up to 30 mg kg-' for PhCL28A and I00 mg kg-' for SZP). 3 Irrespective of the route of administration, SZP (100mgkg-') and PhCL28A (30mgkg-') 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 (ICm, = 230 nM) was approximatively 480 times more potent than SZP (ICy, = 110 M) against rat stomach cytosolic prostaglandin inactivation.4 Both ETOH (50%, 5 ml kg-', orally) and PBT (200 mg kg-', orally) significantly decreased ex vivo gastric cytosolic prostaglandin inactivation. PhCL28A (30mg kg-', orally or i.p.) decreased prostaglandin inactivation still further after ulcerogen treatment except when given i.p. before ETOH treatment. SZP (100mg kg-') had a similar effect when given orally before PBT treatment. 5When 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-' orally (but not i.p.) produced an 88% increase in prostaglandin E2 (PGE2) levels, but had no effect on 6-keto-PGF,, or thromboxane B2 formation during homogenization. SZP (100mg kg' 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.

Effect of various doses of palm vitamin E and tocopherol on aspirin‐ induced gastric lesions in rats

“…Determination of gastric lesions The gastric mucosa was then exposed by cutting the stomach along the greater curvature, washing with saline and placing on a flat wooden board. The severity of gastric mucosal lesions, expressed as ulcer index, was determined semiquantitatively as described by Berry et al . (1988).…”

“…Determination of gastric lesions The gastric mucosa was then exposed by cutting the stomach along the greater curvature, washing with saline and placing on a flat wooden board. The severity of gastric mucosal lesions, expressed as ulcer index, was determined semiquantitatively as described by Berry et al (1988). The severity of gastric mucosal lesions was graded as follows: 5 multiple ulcers following almost the entire length of the gastric fold, 4 lesions that followed approximately 80% of the folds, 3 ulcers 1±4 mm in length on 80% of the folds, 2 at least two ulcers approximately 2 mm in length, 1 the presence of one ulcer and generalized erythema and 0 no visible damage.…”

Protective Effect ofCratoxylum formosumExtract Against Acid/Alcohol-Induced Gastric Mucosal Damage in Rats

“…The stomach was opened along the greater curvature, rinsed with ice-cold 0.9% NaCl, and extended on the paraffin board by fixing with needles. The mucosal lesion was measured by determination of the bleeding spot, bleeding area, and total mucosal area using an image analyzer (UTHSCSA image tool, version 3.00 [ddsdx.uthscsa.edu=dig=download.html]) as described by Sripanidkulchai et al 11 The severity of gastric mucosal lesions, expressed as the ulcer index, was determined quantitatively as described by Berry et al 24 and graded as follows: 5 ¼ multiple ulcers following almost the entire length of the gastric folds; 4 ¼ lesions that followed approximately 80% of the folds; 3 ¼ ulcers 1-4 mm in length on 80% of the folds; 2 ¼ at least two ulcers of approximately 2 mm in length; 1 ¼ the presence of one ulcer and generalized erythema; or 0 ¼ no visible damage. From these scores the ulcer index was obtained, which is the product of the mean lesion score and the percentage of animals presenting a lesion or lesions.…”

Palm vitamin E and the healing of ethanol-induced gastric lesions

“…The mucosal surface of the stomach was washed with normal saline and laid on a flat wooden board with the mucosal surface facing up. The gastric mucosa was observed for lesions and was graded according to the following scale, previously described but with minor modifications: 16 5 = multiple lesions following almost entire length of gastric folds; 4 = lesions which followed almost 80% of the entire folds; 3 = lesions 1-4 mm in length on 80% of the folds; 2 = at least two lesions approximately 2 mm in length; 1 = the presence of one lesion and generalized erythema; 0.5 = the presence of dot haemorrhages; and 0 = no visible damage.…”