Ghrelin and toxicity: recent findings and future challenges

Vasileiou, Ioanna; Patsouras, Demetrios; Patsouris, Efstratios; Theocharis, Stamatios

doi:10.1002/jat.2803

Cited by 6 publications

(4 citation statements)

References 73 publications

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“…Because the survival increases in Peg-G-CSF-treated RI mice is around 30% above the vehicle-treated counterpart group ( Kiang et al, 2014a ), the object of this project was to investigate remedies that could enhance Peg-G-CSF efficacy in treating RI. Ghrelin was selected for this purpose because this co-therapy has been reported to reduce the RI-induced brain hemorrhage ( Kiang et al, 2019 ; Gorbunov and Kiang, 2021 ) and Ghrelin alone was effective for other organ diseases ( Wynne et al, 2005 ; Vasileious et al, 2013 ; Pereira et al, 2017 ; Fritz et al, 2020 ). Ghrelin is a peptide containing 28 amino acids; it is produced in the stomach during hunger and released into the blood stream to go to the hypothalamus for initiating the desire of food intake ( Wynne et al, 2005 ; Vasileious et al, 2013 ; Pereira et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation

et al. 2021

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Exposure to ionizing radiation (radiation injury, RI) in nuclear-related episode is evident to be life-threatening. RI occurs at levels of organs, tissues, cytosols, or nucleus. Their mechanisms are still not fully understood. FDA approves pegylated granulocyte colony-stimulating factor (Neulasta™, Peg-G-CSF) for acute hematopoietic syndrome and has been shown to save lives after lethal RI. We aimed to test whether Ghrelin enhanced Peg-G-CSF’s efficacy to save more lives after lethal RI. B6D2F1/J female mice were used for the study. They received 9.5 Gy (LD50/30 at 0.4 Gy/min) emitted from the 60Co-γ-photon radiation facility. Peg-G-CSF was injected subcutaneously at 1 mg/kg once on days 1, 8, and 15 after irradiation. Ghrelin contains 28 amino acid and is a hunger peptide that has been shown to stimulate food intake, promote intestinal epithelial cell proliferation, elevates immunity, inhibits brain hemorrhage, and increases stress-coping. Ghrelin was injected subcutaneously at 113 μg/kg once on days 1, 2, and 3 after irradiation. Survival, body weight, water consumption, hematology, spleen weight, splenocytes, bone marrow cells, and histology of bone marrow and ileum were performed. We observed that radiation resulted in 30-days survival by 30%. RI decreased their body weights and water consumption volumes. On the 30th day post-RI, platelets and WBCs such as basophils, eosinophils, monocytes, lymphocytes, neutrophils and leukocytes were still significantly decreased in surviving mice. Likewise, their RBC, hemoglobin, hematocrit, and splenocytes remained low; splenomegaly was found in these mice. Bone marrow in surviving RI animals maintained low cellularity with high counts of fat cells and low counts of megakaryocytes. Meanwhile, ileum histology displayed injury. However, mice co-treated with both drugs 24 h after RI resulted in 30-days survival by 45% above the vehicle group. Additionally, the body-weight loss was mitigated, the acute radiation syndrome was reduced. This co-therapy significantly increased neutrophils, eosinophils, leukocytes, and platelets in circulation, inhibited splenomegaly, and increased bone marrow cells. Histopathological analysis showed significant improvement on bone marrow cellularity and ileum morphology. In conclusion, the results provide a proof of concept and suggest that the co-therapy of Peg-G-CSF and Ghrelin is efficacious to ameliorate RI.

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Section: Introductionmentioning

confidence: 99%

Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation

et al. 2021

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“…Ghrelin is capable of modulating appetite, energy and glucose metabolism, gastrointestinal, immune and cardiovascular functions and cell proliferation (Leite-Moreira and Soares, 2007). It is also implicated in many pathogeneses such as type II diabetes based on the modification in either its receptor concentration or expression (Bolkent et al, 2006;Vasileiou et al, 2013). Obestatin is a 23-amino-acid-peptide derived from the carboxy-terminal part of the ghrelin gene.…”

Section: Introductionmentioning

confidence: 99%

The role of ghrelin on apoptosis, cell proliferation and oxidant‐antioxidant system in the liver of neonatal diabetic rats

Koyutürk

Saçan

Karabulut

et al. 2015

Cell Biology International

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Ghrelin is a multifunctional peptide hormone which stimulates appetite and regulates glucose metabolism and adipogenesis. The purpose of this study was to investigate whether ghrelin has protective effects in the liver of streptozocin (STZ) diabetic rats or not. Wistar-type neonatal rats were divided into four groups: I. Controls, II. Ghrelin administrated controls, III. STZ-diabetic rats, and IV. Ghrelin administrated diabetic rats. On the second day after birth, 100 mg/kg STZ was administered intraperitoneally in a single dose to induce diabetes in rats. 100 µg/kg/day ghrelin was administrated to rats subcutaneously for 4 weeks. Ghrelin administration improved histopathologic changes in STZ-diabetic liver. Obestatin immunoreactivity has been shown in livers of neonatal rats. The immunoreactivity of obestatin increased in diabetic rats and a decline was observed in ghrelin administrated diabetic rats. Caspase 8 and 3 immunoreactivities increased in diabetic rats; however, ghrelin administration differently affected caspases 8 and 3 immunoreactivities. Proliferating cell nuclear antigen immunoreactivities decreased in diabetic rats and in ghrelin administrated diabetic rats. Serum alanine (P < 0.05) and aspartate transaminase (P < 0.0001) and serum alkaline phosphatase (P < 0.0001) activities were decreased in ghrelin administrated diabetic rats compared to the diabetic rats. Gamma glutamyl transferase activity (P < 0.001) decreased in ghrelin administrated diabetic rats compared to the diabetic rats. The response of antioxidants including glutathione levels, catalase and superoxide dismutase activities were altered in ghrelin administrated diabetic rats. Our findings indicate that ghrelin administration affects hepatic functions in neonatal diabetic rats and might be considered as a therapeutic agent.

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“…Ghrelin has several physiological functions, including secretion of GH ( Kojima et al , 1999 ; Nagaya et al , 2001 ) and insulin-like growth factor-1 (IGF-1; Akamizu and Kangawa, 2006 ; Veldhuis et al , 2008 ), promotion of the appetite signal, and stimulation of gastrointestinal activity in humans ( Takata et al , 2015a ). In addition, both in vivo and in vitro studies have shown that ghrelin, via promoting IGF-1 release, exerts a powerful protective effect against damage of the heart, gastrointestinal tract, liver, nervous system, and kidney ( Gobe et al , 1999 ; Takeda et al , 2006 ; Vasileiou et al , 2013 ).…”

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confidence: 99%

Improvement of cisplatin-related renal dysfunction by synthetic ghrelin: a prospective randomised phase II trial

et al. 2016

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Background:Ghrelin, a 28-amino acid peptide predominantly produced by the stomach, exerts powerful renal protective effects by increasing levels of insulin-like growth factor-1 (IGF-1). The aim of this study was to evaluate the effects of ghrelin on the incidence of renal dysfunction in patients receiving cisplatin-based chemotherapy.Methods:Forty patients with oesophageal cancer receiving cisplatin-based chemotherapy were assigned to either the ghrelin group (n=20), which received ghrelin (0.5 μg kg−1 h−1) for 5 days, or a placebo group (n=20). The primary endpoint was serum creatinine. Secondary endpoints were serum cystatin C, chemotherapy-related adverse events, changes in serum ghrelin-related hormone levels, correlation between markers of renal injury and hormone concentrations, and effects on the second cycle of chemotherapy.Results:Blood acyl ghrelin, total ghrelin, and IGF-1 concentrations on day 4 were significantly higher in the ghrelin group. The renal dysfunction, serum creatinine and cystatin C levels, dose reduction, and delay in the initiation of the second cycle of chemotherapy were lower in the ghrelin group than in the control group. Serum creatinine levels were significantly correlated with serum IGF-1 levels.Conclusion:Continuous synthetic ghrelin administration during cisplatin-based chemotherapy attenuated renal dysfunction and harmful effects on subsequent chemotherapy, possibly by increasing IGF-1 levels.

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Ghrelin and toxicity: recent findings and future challenges

Cited by 6 publications

References 73 publications

Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation

Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation

The role of ghrelin on apoptosis, cell proliferation and oxidant‐antioxidant system in the liver of neonatal diabetic rats

Improvement of cisplatin-related renal dysfunction by synthetic ghrelin: a prospective randomised phase II trial

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