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

Ludmila Filaretova, Tatiana Bagaeva, G. Makara

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Our previous investigations suggest that the reduction of stress-induced corticosterone release, or inhibition of corticosterone actions, promotes stress-induced gastric erosions in rats. In this study the effect of glucocorticoid deficiency on susceptibility to gastric mucosal injury by nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated in rats. Gastric erosions induced in male rats by indomethacin (25 mg/kg sc) or acidified aspirin (40 mM po) were studied one week after adrenalectomy with or without corticosterone replacement or after occupation of glucocorticoid receptors by the antagonist RU-38486 during the period of erosion formation. Corticosterone for replacement (4 mg/kg sc) was injected 15 min before the administration of indomethacin or acidified aspirin to adrenalectomized rats. The antagonist RU-38486 (10 mg/kg po) was administered twice, 20 min before and 60 min after NSAID administration. Plasma corticosterone levels were measured by fluorometry. Gastric erosions were quantitated by measuring the area of damage. Indomethacin or acidified aspirin induced both plasma corticosterone rise and gastric erosions. Adrenalectomy decreased both basal and NSAID-induced corticosterone levels and markedly promoted gastric erosion formation caused by the NSAID. An acute corticosterone replacement mimicking indomethacin-and aspirin-induced corticosterone rise prevented the effect of adrenalectomy on the gastric erosions. The administration of the glucocorticoid/progesterone antagonist RU-38486 significantly potentiated the formation of gastric erosions induced by indomethacin as well as aspirin. These observations suggest a gastroprotective action of glucocorticoids released in response to NSAID treatment against NSAID-induced injury.

Original languageEnglish
Pages (from-to)2457-2468
Number of pages12
JournalLife Sciences
Volume71
Issue number21
DOIs
Publication statusPublished - Oct 11 2002

Fingerprint

Glucocorticoid Receptors
Corticosterone
Glucocorticoids
Rats
Anti-Inflammatory Agents
Erosion
Stomach
Indomethacin
Aspirin
Pharmaceutical Preparations
Mifepristone
Adrenalectomy
Plasmas
Drug therapy
Fluorometry
Wounds and Injuries
Occupations
Progesterone

Keywords

  • Acidified aspirin
  • Gastric erosions
  • Glucocorticoids
  • Indomethacin
  • RU-38486

ASJC Scopus subject areas

  • Pharmacology

Cite this

Aggravation of nonsteroidal antiinflammatory drug gastropathy by glucocorticoid deficiency or blockade of glucocorticoid receptors in rats. / Filaretova, Ludmila; Bagaeva, Tatiana; Makara, G.

In: Life Sciences, Vol. 71, No. 21, 11.10.2002, p. 2457-2468.

Research output: Contribution to journalArticle

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