2. Academic Validation
  3. Protective effects of growth hormone-releasing hormone analogs in DSS-induced colitis in mice

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

  • Sci Rep. 2021 Jan 28;11(1):2530. doi: 10.1038/s41598-021-81778-4.
Lucia Recinella 1,  Annalisa Chiavaroli 1,  Valentina Di Valerio 2,  Serena Veschi 1,  Giustino Orlando 1,  Claudio Ferrante 1,  Iacopo Gesmundo 3,  Riccarda Granata 3,  Renzhi Cai 4 5 6,  Wei Sha 4 5 6,  Andrew V Schally 4 5 6,  Rossano Lattanzio 7 8,  Luigi Brunetti 9,  Sheila Leone 10
Affiliations

Affiliations

  • 1 Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy.
  • 2 Department of Medicine and Ageing Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
  • 3 Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Turin and Città Della Salute e Della Scienza Hospital, Turin, Italy.
  • 4 Veterans Affairs Medical Center, Miami, FL, 33125, USA.
  • 5 Division of Endocrinology, Diabetes and Metabolism, and Division of Medical/Oncology, Department of Medicine, and Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA.
  • 6 Sylvester Comprehensive Cancer Center, Miami, FL, 33136, USA.
  • 7 Department of Medical, Oral and Biotechnological Sciences, G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
  • 8 Center for Advanced Studies and Technology (CAST), G. d'Annunzio University of Chieti-Pescara, Chieti, Italy.
  • 9 Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy. luigi.brunetti@unich.it.
  • 10 Department of Pharmacy, G. d'Annunzio University of Chieti-Pescara, Via dei Vestini 31, 66100, Chieti, Italy. sheila.leone@unich.it.
PMID: 33510215 DOI: 10.1038/s41598-021-81778-4
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.

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