Dexamethasone makes the gastric mucosa susceptible to ulceration by inhibiting prostaglandin synthetase and peroxidase--two important gastroprotective enzymes.
The plausible mechanism by which dexamethasone makes the gastric mucosa susceptible to ulceration has been studied. As acid aggravates ulcer, the role of dexamethasone on acid secretion was first investigated. Dexamethasone stimulates both basal and drug (mercaptomethylimidazole)-induced gastric acid secretion by 100 and 50% respectively in male Wister rats 24 h after intramuscular administration at the dose of 1 mg/kg body wt. This stimulated acid secretion is 93% blocked by cimetidine indicating increased liberation of histamine in the process. Pretreatment of dexamethasone before 24 h produces ulcer in 30% of the pylorus- ligated rats and aggravates the ulcer index by 82% in both pylorus and esophagus ligated rats. The incidence of ulceration in the latter cases is also increased by 25%. As mucosal prostaglandin synthetase and peroxidase play an important role in gastroprotection through biosynthesis of prostaglandin and by scavenging endogenous H2O2 respectively, the effect of dexamethasone on the activities of these gastroprotective enzymes were studied. Prostaglandin synthetase and peroxidase activities of the mucosa are significantly inhibited by 87 and 83% respectively by 24-h pretreatment with dexamethasone. The results indicate that dexamethasone makes the mucosa prone to ulceration by inhibiting the activity of prostaglandin synthetase to block the gastroprotective action of prostaglandin and also by inhibiting the peroxidase, thereby elevating the endogenous H2O2 level to generate more reactive hydroxyl radical responsible for the mucosal damage.
Bandyopadhyay
U
U
Department of Physiology, Indian Institute of Chemical Biology, Calcutta, India.
Biswas
K
K
Bandyopadhyay
D
D
Ganguly
C K
CK
Banerjee
R K
RK
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006636:Histamine Release / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D010434:Pepsin A / Q000032:analysis; D010544:Peroxidases / Q000037:antagonists & inhibitors*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000209:etiology / Q000503:physiopathology*
C107674:2-mercapto-1-methylimidazole; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D003907:Dexamethasone; D002927:Cimetidine; D010544:Peroxidases; D011451:Prostaglandin-Endoperoxide Synthases; D010434:Pepsin A