Abstract
Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.
Highlights
Ghrelin, a 28-amino acid peptide, was originally isolated from rat and human stomach by Kojima et al in 1999 [1]
The form of evidence showing that the therapeutic effect of ghrelin in the course of colitis depends on the release of endogenous growth hormone and insulin-like growth factor-1 (IGF-1) was obtained in hypophysectomized rats treated with ghrelin
Treatment with ghrelin was without any effect on mucosal DNA synthesis in the colon of hypophysectomized rats. These findings indicate that the ghrelin-induced stimulation of DNA synthesis and growth-promoting effect are related to the release of endogenous growth hormone and IGF-1
Summary
A 28-amino acid peptide, was originally isolated from rat and human stomach by Kojima et al in 1999 [1]. The form of evidence showing that the therapeutic effect of ghrelin in the course of colitis depends on the release of endogenous growth hormone and IGF-1 was obtained in hypophysectomized rats treated with ghrelin. Our present study showed that apart from the acceleration of mucosal damage healing, other mechanisms of therapeutic effect of ghrelin in colitis are associated with the release of endogenous growth hormone and IGF-1. Experiments performed on hypophysectomized rats indicated that the anti-inflammatory effect of ghrelin in acetic acid-induced colitis is related to the release of endogenous growth hormone and IGF-1. Administration of ghrelin was without any effect on mucosal blood flow in the colon in hypophysectomized rats These observations indicate that the ghrelin-evoked improvement of blood flow in colonic mucosa in pituitary-intact rats with colitis is dependent on the release of endogenous growth hormone and IGF-1. It is impossible to ascertain whether the therapeutic effect of ghrelin after application of antibodies against growth hormone and IGF-1 is independent of the above hormonal factors or is the result of insufficient elimination of growth hormone and IGF-1 from the body
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