Mechanisms by which endogenous glucocorticoid protects against indomethacin-induced gastric injury in rats.
We investigated the mechanisms underlying the protective action of glucocorticoids against indomethacin-induced gastric lesions. One-week adrenalectomized rats with or without corticosterone replacement (4 mg/kg sc) were administered indomethacin (25 mg/kg sc), and gastric secretion (acid, pepsin, and mucus), motility, microvascular permeability, and blood glucose levels were examined. Indomethacin caused gastric lesions in sham-operated rats, with an increase in gastric motility and microvascular permeability as well as a decrease in mucus secretion. Adrenalectomy significantly worsened the lesions and potentiated these functional disorders. Glucose levels were lowered by indomethacin in sham-operated rats, and this response was enhanced by adrenalectomy. The changes observed in adrenalectomized rats were prevented by supplementations of corticosterone at a dose mimicking the indomethacin-induced rise in corticosterone, whereas the protective effect of corticosterone was attenuated by RU-38486, a glucocorticoid receptor antagonist. We conclude that the gastroprotective action of endogenous glucocorticoids may be provided by their support of glucose homeostasis and inhibitory effects on enhanced gastric motility and microvascular permeability as well as maintaining the production of mucus.
Filaretova
Ludmila
L
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan.
Tanaka
Akiko
A
Miyazawa
Tohru
T
Kato
Shinichi
S
Takeuchi
Koji
K
D000315:Adrenalectomy; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001786:Blood Glucose / Q000032:analysis; D002199:Capillary Permeability / Q000187:drug effects; D005744:Gastric Acid / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007213:Indomethacin / Q000009:adverse effects*; D008297:Male; D009093:Mucus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D013272:Stomach Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D013276:Stomach Ulcer / Q000139:chemically induced
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001786:Blood Glucose; D005938:Glucocorticoids; D007213:Indomethacin