Role of ghrelin on growth hormone/insulin-like growth factor-1 axis during endotoxemia

Faim, Felipe de Lima; Passaglia, Patrícia; Batalhão, Marcelo Eduardo; Lacchini, Riccardo; Stabile, Angelita Maria; Cárnio, Evelin Capellari

doi:10.1016/j.ghir.2019.08.004

Cited by 12 publications

(11 citation statements)

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“…In another rat model, treatment with ghrelin after CLP increased the expression of autophagy-associated proteins. This further supports that ghrelin protects intestinal mucosa from sepsis injury (117)(118)(119)(120)(121).…”

Section: Effect Of Ghrelin On Gastrointestinal System In Sepsissupporting

confidence: 76%

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Ghrelin as an Anti-Sepsis Peptide: Review

et al. 2021

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Sepsis continues to produce widespread inflammation, illness, and death, prompting intensive research aimed at uncovering causes and therapies. In this article, we focus on ghrelin, an endogenous peptide with promise as a potent anti-inflammatory agent. Ghrelin was discovered, tracked, and isolated from stomach cells based on its ability to stimulate release of growth hormone. It also stimulates appetite and is shown to be anti-inflammatory in a wide range of tissues. The anti-inflammatory effects mediated by ghrelin are a result of both the stimulation of anti-inflammatory processes and an inhibition of pro-inflammatory forces. Anti-inflammatory processes are promoted in a broad range of tissues including the hypothalamus and vagus nerve as well as in a broad range of immune cells. Aged rodents have reduced levels of growth hormone (GH) and diminished immune responses; ghrelin administration boosts GH levels and immune response. The anti-inflammatory functions of ghrelin, well displayed in preclinical animal models of sepsis, are just being charted in patients, with expectations that ghrelin and growth hormone might improve outcomes in patients with sepsis.

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Section: Effect Of Ghrelin On Gastrointestinal System In Sepsissupporting

confidence: 76%

“…Ghrelin administration in a mouse model induced angiogenesis and neurogenesis in the hippocampus (136). After CLP in rats, FIGURE 3 | Ghrelin and its effect on various organs during sepsis (110)(111)(112)(113)(114)(115)(116)(117)(118)(119)(120)(121)(122)(123)(124)(125)(126).…”

Section: Ghrelin Effects On Cognition In Sepsismentioning

confidence: 99%

Ghrelin as an Anti-Sepsis Peptide: Review

et al. 2021

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“…Ghrelin, involved in appetite stimulation, increases in the plasma of septic patients (Nikitopoulou et al , ), and active ghrelin levels are inversely correlated with the SOFA organ dysfunction score and length of ICU stay. In short‐term preclinical models of sepsis, ghrelin has been shown to decrease pro‐inflammatory cytokine levels, stimulate proliferation of T cells, and attenuate the decrease in serum levels of IGF‐1 (Faim et al , ); however, we found that ghrelin infusion in a long‐term rodent fecal peritonitis model had no impact on outcomes (Hill et al , ). Plasma insulin levels are variably reported as raised or depressed in sepsis, but insulin resistance is commonplace regardless, with subsequent hyperglycemia‐inducing toxicity.…”

Section: Sepsis: a New Who Global Health Prioritymentioning

confidence: 62%

Sepsis therapies: learning from 30 years of failure of translational research to propose new leads

2020

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Sepsis has been identified by the World Health Organization (WHO) as a global health priority. There has been a tremendous effort to decipher underlying mechanisms responsible for organ failure and death, and to develop new treatments. Despite saving thousands of animals over the last three decades in multiple preclinical studies, no new effective drug has emerged that has clearly improved patient outcomes. In the present review, we analyze the reasons for this failure, focusing on the inclusion of inappropriate patients and the use of irrelevant animal models. We advocate against repeating the same mistakes and propose changes to the research paradigm. We discuss the long‐term consequences of surviving sepsis and, finally, list some putative approaches—both old and new—that could help save lives and improve survivorship.

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“…RNA was quantified by spectrophotometry using nanodrop 1000 equipment (Thermo Fisher Scientific, Wilmington, DE, USA). The analysis of the genes of interest was performed by RT-PCR using TaqMan assays ( AVP Rn00690189_g1; corticotropin-releasing hormone- CRH Rn01462137_m1; TNF Rn99999017_m1; IL10 Rn01483988_g1; inducible nitric oxide synthase ( NOS2 ) Rn00561646_m1; GAPDH Rn01775763_g1) as previously described in Faim et al [ 28 ]. The results were expressed as normalized relative quantities (NRQ).…”

Section: Methodsmentioning

confidence: 99%

Central Administration of Angiotensin-(1-7) Improves Vasopressin Impairment and Hypotensive Response in Experimental Endotoxemia

Passaglia

Faim

Batalhão

et al. 2021

Cells

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Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor is a counter-regulatory axis that counteracts detrimental renin-angiotensin system (RAS) effects, especially regarding systemic inflammation, vasopressin (AVP) release, and hypothalamic-pituitary-adrenal (HPA) activation. However, it is not completely understood whether this system may control centrally or systemically the late phase of systemic inflammation. Thus, the aim of this study was to determine whether intracerebroventricular (i.c.v.) administration of Ang-(1-7) can modulate systemic inflammation through the activation of humoral pathways in late phase of endotoxemia. Endotoxemia was induced by systemic injection of lipopolysaccharide (LPS) (1.5 mg/kg, i.v.) in Wistar rats. Ang-(1-7) (0.3 nmol in 2 µL) promoted the release of AVP and attenuated interleukin-6 (IL-6) and nitric oxide (NO) levels but increased interleukin-10 (IL-10) in the serum of the endotoxemic rats. The central administration of Mas receptor antagonist A779 (3 nmol in 2 µL, i.c.v.) abolished these anti-inflammatory effects in endotoxemic rats. Furthermore, Ang-(1-7) applied centrally restored mean arterial blood pressure (MABP) without affecting heart rate (HR) and prevented vascular hyporesponsiveness to norepinephrine (NE) and AVP in animals that received LPS. Together, our results indicate that Ang-(1-7) applied centrally promotes a systemic anti-inflammatory effect through the central Mas receptor and activation of the humoral pathway mediated by AVP.

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Role of ghrelin on growth hormone/insulin-like growth factor-1 axis during endotoxemia

Cited by 12 publications

References 50 publications

Ghrelin as an Anti-Sepsis Peptide: Review

Ghrelin as an Anti-Sepsis Peptide: Review

Sepsis therapies: learning from 30 years of failure of translational research to propose new leads

Central Administration of Angiotensin-(1-7) Improves Vasopressin Impairment and Hypotensive Response in Experimental Endotoxemia

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