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

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 p...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/182f84ae73e34728bf37d0224ab8d8f7
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spelling	oai:doaj.org-article:182f84ae73e34728bf37d0224ab8d8f72021-12-02T13:24:36ZProtective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice10.1038/s41598-021-81778-42045-2322https://doaj.org/article/182f84ae73e34728bf37d0224ab8d8f72021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81778-4https://doaj.org/toc/2045-2322Abstract 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.Lucia RecinellaAnnalisa ChiavaroliValentina Di ValerioSerena VeschiGiustino OrlandoClaudio FerranteIacopo GesmundoRiccarda GranataRenzhi CaiWei ShaAndrew V. SchallyRossano LattanzioLuigi BrunettiSheila LeoneNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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 Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
description	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.
format	article
author	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
author_facet	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
author_sort	Lucia Recinella
title	Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
title_short	Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
title_full	Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
title_fullStr	Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
title_full_unstemmed	Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice
title_sort	protective effects of growth hormone-releasing hormone analogs in dss-induced colitis in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/182f84ae73e34728bf37d0224ab8d8f7
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Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice

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