Influence of Adrenalectomy on Protective Effects of Urocortin I, a Corticotropin-Releasing Factor, Against Indomethacin-Induced Enteropathy in Rats

Abstract

We examined the influence of adrenalectomy on NSAID-induced small intestinal damage in rats and investigated the possible involvement of adrenal glucocorticoids in the protective effects of urocortin I, a corticotropin-releasing factor (CRF) agonist. Male SD rats without fasting were administered indomethacin s.c. and killed 24 h later in order to examine the hemorrhagic lesions that developed in the small intestine. Urocortin I (20 µg/kg) was given i.v. 10 min before the administration of indomethacin. Bilateral adrenalectomy was performed a week before the experiment. Indomethacin (10 mg/kg) caused multiple hemorrhagic lesions in the small intestine, which were accompanied by a decrease in mucus secretion and increases in intestinal motility, enterobacterial invasion, and iNOS expression. Adrenalectomy markedly increased the ulcerogenic and motility responses caused by indomethacin, with further enhancements in bacterial invasion and iNOS expression; severe lesions occurred at 3 mg/kg, a dose that did not induce any damage in sham-operated rats. This worsening effect was also observed by the pretreatment with mifepristone (a glucocorticoid receptor antagonist). Urocortin I prevented indomethacin-induced enteropathy, and this effect was completely abrogated by the pretreatment with astressin 2B, a CRF2 receptor antagonist, but was not significantly affected by either adrenalectomy or the mifepristone pretreatment. These results suggested that adrenalectomy aggravated the intestinal ulcerogenic response to indomethacin, the intestinal hypermotility response may be a key element in the mechanism for this aggravation, and endogenous glucocorticoids played a role in intestinal mucosal defense against indomethacin-induced enteropathy, but did not account for the protective effects of urocortin I, which were mediated by the activation of peripheral CRF2 receptors

A Comparative Histological Study on the Effect of Adipose-Derived Stem Cells versus Their Conditioned Medium on Indomethacin Induced Enteritis in Adult Female Albino Rats

“…This could be explained by ulceration of the mucosa and destruction of both villi and crypts by indomethacin. This finding was in accordance, with other authors who attributed this to enterobacterial invasion, upregulation ofinducible nitric oxide synthase (iNOS) expression and overproduction of nitric oxide (NO) in the mucosa [48,49] . In addition, the present work revealed significant decrease in the mean optical density of the mucus in group II, III and VI compared to control group.…”

Influence of adrenalectomy on protective effects of urocortin I, a corticotropin-releasing factor (CRF)-related peptide, against indomethacin-induced enteropathy in rats

“…However, since dexamethasone inhibits indo-methacin-induced enteropathy (Takeuchi, Satoh 2015), it is possible that protective effects of urocortin may be, at least in part, mediated by endogenous glucocorticoids released from the adrenal gland through activation of peripheral CRF receptors. The present study examines the influences of bilateral adrenalectomy and mifepristone, a glucocorticoid receptor antagonist, on indomethacin-induced enteropathy in rats in order to investigate possible involvement of adrenal glucocorticoids in the protective effects of urocortin I (Takeuchi et al 2016).…”

EDITORIAL (Thematic Issue: Brain Gut Axis-New View)

“…Naoko Abe, Aiko Kumano, and Koji Takeuchi [6] examined the influence of adrenalectomy on NSAID-induced small intestinal damage in rats and investigated the possible involvement of adrenal glucocorticoids in the protective effects of urocortin I (a corticotropin-releasing factor agonist). Their results suggest that adrenalectomy aggravated the intestinal ulcerogenic response to indomethacin, and endogenous glucocorticoids played a role in intestinal mucosal defense against indomethacin-induced enteropathy, but did not account for the protective effects of urocortin I, which were mediated by the activation of peripheral corticotropin-releasing factor 2 receptors [6].…”

“…Their results suggest that adrenalectomy aggravated the intestinal ulcerogenic response to indomethacin, and endogenous glucocorticoids played a role in intestinal mucosal defense against indomethacin-induced enteropathy, but did not account for the protective effects of urocortin I, which were mediated by the activation of peripheral corticotropin-releasing factor 2 receptors [6]. …”