Glucocorticoid-induced gastric mucosal damage: inhibition of leukotriene, but not prostaglandin biosynthesis.
The effects of daily administration of ulcerogenic doses of the glucocorticoids, dexamethasone and prednisolone, on gastric prostaglandin and leukotriene synthesis were examined in the rat. Significant gastric damage was not observed until the fourth day of treatment with dexamethasone and until the sixth day of treatment with prednisolone. However, the onset of gastric damage was not accompanied by any significant effect of these drugs on gastric 6-keto prostaglandin Fl alpha synthesis. Conversely, both drugs caused a reduction in gastric leukotriene C4 synthesis, with dexamethasone producing a highly significant (p less than 0.001) effect. Furthermore, there was a highly significant (p less than 0.001) correlation between the ability of these drugs to inhibit gastric leukotriene C4 synthesis, and their ability to reduce gastric tissue levels of the neutrophilic enzyme myeloperoxidase. Thus, glucocorticoid-induced gastric damage does not appear to be related to inhibitory effects of these drugs on prostaglandin synthesis. Whether or not effects of these drugs on gastric leukotriene C4 synthesis and myeloperoxidase activity are relevant to the mechanism of ulceration is unclear.
Wallace
J L
JL
Department of Physiology, Queen's University, Kingston, Ontario, Canada.
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000187:drug effects*; D008297:Male; D009195:Peroxidase / Q000032:analysis; D011239:Prednisolone / Q000494:pharmacology / Q000633:toxicity*; D011460:Prostaglandins F / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000096:biosynthesis*; D013997:Time Factors
D011460:Prostaglandins F; D013189:SRS-A; D003907:Dexamethasone; D011239:Prednisolone; D009195:Peroxidase