Molecular Ghrelin System in the Pancreatic Acinar Cells: The Role of the Polypeptide, Caerulein and Sensory Nerves

Ceranowicz

et al. 2017

IJMS

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Ghrelin was shown to exhibit protective and therapeutic effect in the gut. Aim of the study was to investigate the role of sensory nerves (SN) in the protective effect of ghrelin in acute pancreatitis (AP). Studies were performed on male Wistar rats or isolated pancreatic acinar cells. After capsaicin deactivation of sensory nerves (CDSN) or treatment with saline, rats were pretreated intraperitoneally with ghrelin or saline. In those rats, AP was induced by cerulein or pancreases were used for isolation of pancreatic acinar cells. Pancreatic acinar cells were incubated in cerulein-free or cerulein containing solution. In rats with intact SN, pretreatment with ghrelin led to a reversal of the cerulein-induced increase in pancreatic weight, plasma activity of lipase and plasma concentration of tumor necrosis factor-α (TNF-α). These effects were associated with an increase in plasma interleukin-4 concentration and reduction in histological signs of pancreatic damage. CDSN tended to increase the severity of AP and abolished the protective effect of ghrelin. Exposure of pancreatic acinar cells to cerulein led to increase in cellular expression of mRNA for TNF-α and cellular synthesis of this cytokine. Pretreatment with ghrelin reduced this alteration, but this effect was only observed in acinar cells obtained from rats with intact SN. Moreover, CDSN inhibited the cerulein- and ghrelin-induced increase in gene expression and synthesis of heat shock protein 70 (HSP70) in those cells. Ghrelin exhibits the protective effect in cerulein-induced AP on the organ and pancreatic acinar cell level. Sensory nerves ablation abolishes this effect.

Section: Methodsmentioning

confidence: 99%

Capsaicin-Sensitive Sensory Nerves Are Necessary for the Protective Effect of Ghrelin in Cerulein-Induced Acute Pancreatitis in Rats

Bonior

Ceranowicz

et al. 2017

IJMS

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“…It accelerated the healing of oral [ 55 , 56 ], gastric [ 57 ], and duodenal [ 55 , 57 ] ulcers, and colonic inflammation [ 58 , 59 , 60 , 61 , 62 ]. Ghrelin also exhibited a therapeutic effect in animal models of acute pancreatitis [ 63 , 64 , 65 , 66 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment with Obestatin—A Ghrelin Gene-Encoded Peptide—Reduces the Severity of Experimental Colitis Evoked by Trinitrobenzene Sulfonic Acid

Konarska

Cieszkowski

et al. 2018

IJMS

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Obestatin is a 23-amino acid peptide derived from proghrelin, a common prohormone for ghrelin and obestatin. Previous studies showed that obestatin exhibited some protective and therapeutic effects in the gut. The aim of our presented study was to examine the effect of treatment with obestatin on trinitrobenzene sulfonic acid (TNBS)-induced colitis. In rats anesthetized with ketamine, colitis was induced through intrarectal administration of 25 mg of 2,4,6-trinitrobenzene sulfonic acid (TNBS). Obestatin was administered intraperitoneally at doses of 4, 8, or 16 nmol/kg, twice per day for four consecutive days. The first dose of obestatin was given one day before the induction of colitis, and the last one was given two days after administration of TNBS. Fourteen days after the induction of colitis, rats were anesthetized again with ketamine, and the severity of colitis was determined. The administration of obestatin had no effect on the parameters tested in rats without the induction of colitis. In rats with colitis, administration of obestatin at doses of 8 or 16 nmol/kg reduced the area of colonic damage, and improved mucosal blood flow in the colon. These effects were accompanied by a reduction in the colitis-evoked increase in the level of blood leukocytes, and mucosal concentration of pro-inflammatory interleukin-1β. Moreover, obestatin administered at doses of 8 or 16 nmol/kg reduced histological signs of colonic damage. The administration of obestatin at a dose of 4 nmol/kg failed to significantly affect the parameters tested. Overall, treatment with obestatin reduced the severity of TNBS-induced colitis in rats. This effect was associated with an improvement in mucosal blood flow in the colon, and a decrease in local and systemic inflammatory processes.

“…On the other hand, the administration of ghrelin, in animals before the isolation of acinar cells, led to an increase in the expression of ghrelin and the ghrelin receptor in these isolated cells and reversed the cerulein-induce inhibition of their expression. The same effect was observed in AR42J cells after incubation with cerulein and a ghrelin or combination thereof [240]. In addition, studies performed on rats indicate that capsaicin-sensitive sensory nerves are necessary for the protective effect of ghrelin in cerulein-induced acute pancreatitis [241].…”

Section: Protective Therapeutic and Anti-inflammatory Effects Of mentioning

confidence: 67%

“…In addition, it was demonstrated that endogenous growth hormone and IGF-1 play an essential role in the therapeutic effect of ghrelin in acute pancreatitis [239]. Furthermore, in vitro studies performed on isolated rat acinar cells or rat pancreatic acinar tumor cell line AR42J have shown that the incubation of these cells with cerulein reduces the expression of ghrelin and the ghrelin receptor at the mRNA and protein levels [240]. On the other hand, the administration of ghrelin, in animals before the isolation of acinar cells, led to an increase in the expression of ghrelin and the ghrelin receptor in these isolated cells and reversed the cerulein-induce inhibition of their expression.…”

Section: Protective Therapeutic and Anti-inflammatory Effects Of mentioning

confidence: 99%

Potential Therapeutic Effects of Gut Hormones, Ghrelin and Obestatin in Oral Mucositis

Stempniewicz

Ceranowicz

2019

IJMS

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Chemotherapy and/or head and neck radiotherapy are frequently associated with oral mucositis. Oral pain, odynophagia and dysphagia, opioid use, weight loss, dehydration, systemic infection, hospitalization and introduction of a feeding tube should be mentioned as the main determinated effect of oral mucositis. Oral mucositis leads to a decreased quality of life and an increase in treatment costs. Moreover, oral mucositis is a life-threatening disease. In addition to its own direct life-threatening consequences, it can also lead to a reduced survival due to the discontinuation or dose reduction of anti-neoplasm therapy. There are numerous strategies for the prevention or treatment of oral mucositis; however, their effectiveness is limited and does not correspond to expectations. This review is focused on the ghrelin and obestatin as potentially useful candidates for the prevention and treatment of chemo- or/and radiotherapy-induced oral mucositis.