Dexamethasone‐induced gastric mucosal damage in the rat: possible role of platelet‐activating factor

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Abstract
1 The aim of the present experiments was to study the possible role of platelet-activating factor (PAF) in mediating gastric mucosal damage induced by dexamethasone in the rat by measuring gastric tissue levels of PAF during dexamethasone-treatment and by investigating the effects of specific PAF receptor antagonists on dexamethasone-induced gastric lesions. PAF-like bioactivity extracted from the rat glandular stomach was determined by a platelet aggregation assay. 2 Dexamethasone treatment (0.4– 4 mg kg−1, daily for 1– 6 days) produced time- and dose-dependent damage to the glandular mucosa of the stomach as characterized by extensive, uniform hyperaemia with multiple, focal petechiae and erosions. 3 These changes were accompanied by a time-, and dose-dependent increase in PAF content of the glandular stomach. Control rat stomach contained small amounts of PAF (0.14 ± 0.04 ng per g wet weight), which increased over 40 fold in response to dexamethasone treatment (4 mg kg−1, daily for 6 consecutive days). The presence of PAF-like material in the stomach extract was ascertained by thin-layer chromatography, high performance liquid chromatography and by alkaline hydrolysis. 4 Pretreatment of the animals with one or other of the structurally unrelated PAF receptor antagonists, BN 52021 (10 mg kg−1, i.p.) or BN 50727 (1 mg kg−1, i.p.) significantly reduced dexamethasone-induced gastric damage. In these animals neither petechiae nor erosions were observed. 5 These observations suggest that PAF is a likely endogenous mediator of glucocorticoid-induced gastric mucosal damage in the rat.