Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice

Bibliographic Details
Title: Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
Authors: Lucia Recinella, Annalisa Chiavaroli, Valentina Di Valerio, Serena Veschi, Giustino Orlando, Claudio Ferrante, Iacopo Gesmundo, Riccarda Granata, Renzhi Cai, Wei Sha, Andrew V. Schally, Rossano Lattanzio, Luigi Brunetti, Sheila Leone
Source: Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
Publisher Information: Nature Portfolio, 2021.
Publication Year: 2021
Collection: LCC:Medicine
LCC:Science
Subject Terms: Medicine, Science
More Details: Abstract Besides its metabolic and endocrine effects, growth hormone (GH)-releasing hormone (GHRH) is involved in the modulation of inflammation. Recently synthetized GHRH antagonist MIA-690 and MR-409, GHRH agonist, developed by us have shown potent pharmacological effects in various experimental paradigms. However, whether their administration modify resistance to chronic inflammatory stimuli in colon is still unknown. Ex vivo results demonstrated that MIA-690 and MR-409 inhibited production of pro-inflammatory and oxidative markers induced by lipopolysaccharide on isolated mouse colon specimens. In vivo, both MIA-690 and MR-409 have also been able to decrease the responsiveness to nociceptive stimulus, in hot plate test. Additionally, both peptides also induced a decreased sensitivity to acute and persistent inflammatory stimuli in male mice, in formalin test and dextran sodium sulfate (DSS)-induced colitis model, respectively. MIA-690 and MR-409 attenuate DSS-induced colitis with particular regard to clinical manifestations, histopathological damage and release of pro-inflammatory and oxidative markers in colon specimens. Respect to MR-409, MIA-690 showed higher efficacy in inhibiting prostaglandin (PG)E2, 8-iso-PGF2α and serotonin (5-HT) levels, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and nitric oxide synthase gene expression in colon specimens of DSS-induced colitis. Furthermore, MIA-690 decreased serum insulin-like growth factor (IGF)-1 levels in mice DSS-treated, respect to MR-409. Thus, our findings highlight the protective effects of MIA-690 and MR-409 on inflammation stimuli. The higher antinflammatory and antioxidant activities observed with MIA-690 could be related to decreased serum IGF-1 levels.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-021-81778-4
Access URL: https://doaj.org/article/182f84ae73e34728bf37d0224ab8d8f7
Accession Number: edsdoj.182f84ae73e34728bf37d0224ab8d8f7
Database: Directory of Open Access Journals
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More Details
ISSN:20452322
DOI:10.1038/s41598-021-81778-4
Published in:Scientific Reports
Language:English