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 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.

Antagonist of Growth Hormone-Releasing Hormone Potentiates the Antitumor Effect of Pemetrexed and Cisplatin in Pleural Mesothelioma

“…Elevated expression levels of iNOS and COX-2 in tumor cells is associated with cell proliferation, invasion, resistance to apoptosis and the pathogenesis of different cancers, including mesothelioma [ 59 , 60 , 61 ]. Moreover, the inhibitory role of GHRH antagonists on these inflammatory pathways has been demonstrated in different types of experimental cancers [ 23 , 57 ], as well as inflammatory diseases [ 62 ].…”

Antagonists of Growth Hormone-Releasing Hormone Inhibit the Growth of Pituitary Adenoma Cells by Hampering Oncogenic Pathways and Promoting Apoptotic Signaling

“…The hypothalamic hypophysiotropic neuropeptide growth hormone-releasing hormone (GHRH), in addition to stimulating the release of GH from pituitary somatotrophs, mediated by the pituitary type GHRH receptor (GHRH-R), exerts direct effects in extrapituitary cells and tissues by binding to both GHRH-R and its splice variant 1 (SV1) [8][9][10]. GHRH displays, among others, strong cardioprotective, anti-inflammatory and anxiolytic functions and also acts as a growth factor through autocrine/paracrine mitogenic mechanisms in both nonmalignant and tumor cells [10][11][12][13][14]. This stimulatory loop induced by GHRH can be blocked by GHRH antagonists, leading to the inhibition of tumor growth in experimental models.…”

Protective effects of flavonoids isolated from Agrocybe aegirita on dextran sodium sulfate‐induced colitis

“…Agrocybe aegirita is rich in a variety of active ingredients, such as polysaccharides, amino acids, flavonoids, etc.. Related reports show that flavonoids have certain anti‐inflammatory and antioxidant activities [31,32]. Compared with human ulcerative colitis, DSS‐ induced colitis in mice has certain similarities in pathological manifestations, including hematochezia, weight loss, massive loss of colonic epithelial cells, and infiltration of inflammatory factors [33]. Compared with plant cultivation, Agrocybe aegirita cultivation is relatively low, and only needs a suitable environment and fungus bag, and can be reused [34].…”