Aggravation of nonsteroidal antiinflammatory drug gastropathy by glucocorticoid deficiency or blockade of glucocorticoid receptors in rats

Mechanisms by which endogenous glucocorticoid protects against indomethacin-induced gastric injury in rats

“…The present study confirmed our previous results (7,8,10) demonstrating that endogenous glucocorticoids released in response to indomethacin increase the resistance of the gastric mucosa to the ulcerogenic action of this agent. We further suggested that the gastroprotective action of glucocorticoids against indomethacininduced injury is accounted for by a beneficial effect on defensive factors such as the secretion of mucus and attenuating effects on pathogenic elements such as an increase in gastric motility and microvascular permeability.…”

“…The beneficial effect of an acute elevation in glucocorticoids during NSAID action is the opposite of the well-known ulcerogenic action of longlasting glucocorticoid treatment (14,46). However, the findings support the idea that glucocorticoids released during activation of the hypothalamic-pituitary-adrenocortical (HPA) axis caused by various ulcerogenic stimuli act as a gastroprotective hormone (7,8,10) but not as an ulcerogenic hormone as has generally been accepted for some decades.…”

“…Corticosterone replacement was performed by injecting corticosterone (4 mg/kg) 15 min before the administration of indomethacin to adrenalectomized rats. Our previous results showed that this treatment mimics the indomethacin-induced rise in corticosterone in adrenalectomized rats and prevents the aggravation of gastric lesions in response to indomethacin in these animals (10). In addition, we evaluated whether or not the glucocorticoid antagonist RU-38486 prevents the effect of corticosterone replacement on gastric ulcerogenic and blood glucose responses to indomethacin in adrenalectomized animals.…”

“…During a deficiency of PG, other defensive mechanisms might operate to attenuate NSAID-induced gastropathy, and knowledge of the compensatory mechanisms could be a basis for the creation of new clinical approaches. The results of our previous studies (7,8,10,36) suggested that endogenous glucocorticoids are gastroprotective substances, which play a role as natural defensive factors in maintaining the integrity of the gastric mucosa during NSAID therapy. We have shown that indomethacin and aspirin at ulcerogenic doses induce a rise in corticosterone, which helps the gastric mucosa to resist the harmful actions of these ulcerogenic agents (7,8,10).…”

“…The results of our previous studies (7,8,10,36) suggested that endogenous glucocorticoids are gastroprotective substances, which play a role as natural defensive factors in maintaining the integrity of the gastric mucosa during NSAID therapy. We have shown that indomethacin and aspirin at ulcerogenic doses induce a rise in corticosterone, which helps the gastric mucosa to resist the harmful actions of these ulcerogenic agents (7,8,10). The beneficial effect of an acute elevation in glucocorticoids during NSAID action is the opposite of the well-known ulcerogenic action of longlasting glucocorticoid treatment (14,46).…”