Obestatin Accelerates the Healing of Acetic Acid‐Induced Colitis in Rats

Matuszyk, Aleksandra; Ceranowicz, Piotr; Warzecha, Zygmunt; Cieszkowski, Jakub; Bonior, Joanna; Jaworek, Jolanta; Kuśnierz-Cabała, Beata; Konturek, Peter C.; Ambroży, Tadeusz; Dembiński, Artur

doi:10.1155/2016/2834386

Cited by 36 publications

(36 citation statements)

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“…Previous studies in the gut have shown that reduction in cell proliferation or excessive apoptosis results in the development of ulcers [ 38 , 39 ]. On the other hand, the increase in cell renewal may cause mucosal hyperplasia, but it also leads to increased protection of the digestive system mucosa against the effects of damaging agents, as well as accelerates the reconstruction of mucosa integrity after damage [ 40 , 41 , 42 , 43 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, previous studies have shown that obestatin affects the development and the course of colitis. Pretreatment with obestatin inhibits the development [ 47 ] and accelerates the healing [ 43 ] in acetic acid-induced colitis in rats. Similar protective and therapeutic effect of obestatin has been observed in dextran sodium sulfate (DSS)-induced colitis in rats [ 73 ].…”

Section: Discussionmentioning

confidence: 99%

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Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

Matuszyk

Ceranowicz

Warzecha

et al. 2016

IJMS

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Previous studies have shown that ghrelin reduces colonic inflammation induced by trinitrobenzene sulfonic acid and dextran sodium sulfate. In the present study we determined the effect of treatment with ghrelin on the course of acetic acid-induced colitis in rats. Rectal administration of 3% acetic acid solution led to induction of colitis in all animals. Damage of the colonic wall was accompanied by an increase in mucosal concentration of pro-inflammatory interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), as well mucosal activity of myeloperoxidase. Moreover, induction of colitis led to a reduction in colonic blood flow and DNA synthesis. Administration of ghrelin after induction of colitis led to faster regeneration of the colonic wall and reduction in colonic levels of IL-1β, TNF-α, and myeloperoxidase. In addition, treatment with ghrelin improved mucosal DNA synthesis and blood flow. Our study disclosed that ghrelin exhibits a strong anti-inflammatory and healing effect in acetic acid-induced colitis. Our current observation in association with previous findings that ghrelin exhibits curative effect in trinitrobenzene sulfonic acid- and dextran sodium sulfate-induced colitis suggest that therapeutic effect of ghrelin in the colon is universal and independent of the primary cause of colitis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

Matuszyk

Ceranowicz

Warzecha

et al. 2016

IJMS

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“…The area of colonic mucosa damage was measured using the computerized planimeter (Morphomat, Carl Zeiss, Berlin, Germany), as described previously [27,69]. …”

Section: Methodsmentioning

confidence: 99%

Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis

Ceranowicz

Warzecha

Cieszkowski

et al. 2017

IJMS

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Previous studies have shown that ghrelin exhibits a protective and therapeutic effect in the gut. The aim of the present study was to examine whether administration of ghrelin affects the course of acetic acid-induced colitis and to determine what is the role of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in this effect. In sham-operated or hypophysectomized male Wistar rats, colitis was induced by enema with 1 mL of 3% solution of acetic acid. Saline or ghrelin (given at the dose of 8 nmol/kg/dose) was administered intraperitoneally twice a day. Seven days after colitis induction, rats were anesthetized and the severity of the colitis was assessed. Treatment with ghrelin reduced the area of colonic mucosa damage in pituitary-intact rat. This effect was associated with increase in serum levels of GH and IGF-1. Moreover, administration of ghrelin improved blood flow in colonic mucosa and mucosal cell proliferation, as well as reduced mucosal concentration of proinflammatory interleukin-1β (IL-1β) and activity of myeloperoxidase. Hypophysectomy reduced serum levels of GH and IGF-1 and increased the area of colonic damage in rats with colitis. These effects were associated with additional reduction in mucosal blood follow and DNA synthesis when compared to pituitary-intact rats. Mucosal concentration of IL-1β and mucosal activity of myeloperoxidase were maximally increased. Moreover, in hypophysectomized rats, administration of ghrelin failed to affect serum levels of GH or IGF-1, as well as the healing rate of colitis, mucosal cell proliferation, and mucosal concentration of IL-1β, or activity of myeloperoxidase. We conclude that administration of ghrelin accelerates the healing of the acetic acid-induced colitis. Therapeutic effect of ghrelin in experimental colitis is mainly mediated by the release of endogenous growth hormone and IGF-1.

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“…In addition to its proposed physiological actions, it appears that obestatin may also confer some benefits in GI disease. For example, in rats, obestatin protects against experimental ulcerative colitis via acute attenuation of lipid peroxidation and TH 1 ‐mediated inflammation, chronic suppression of polymorphonuclear leukocyte infiltration, induction of glutathione synthesis, improved mucosal blood flow and stimulation of cell proliferation in colonic mucosa, effects that may be mediated by activation of anti‐inflammatory cytokines (Pamukcu et al ., ; Matuszyk et al ., ). Furthermore, obestatin administration has been shown to confer protective effects against ischaemia–reperfusion injury in rat ileum (Şen et al ., ), whilst the ghrelin/obestatin ratio (but not obestatin levels) is reported to be elevated in patients with active inflammatory bowel diseases (Crohn's disease and colitis) compared with those in remission (Jung et al ., ; Alexandridis et al ., ), suggesting that obestatin signalling may play a role in this setting.…”

Section: Metabolic Actions Of Obestatinmentioning

confidence: 97%

Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes

Cowan

Burch

Green

et al. 2016

British J Pharmacology

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*These two authors contributed equally to this work.Obestatin is a 23-amino acid C-terminally amidated gastrointestinal peptide derived from preproghrelin and which forms an α helix. Although obestatin has a short biological half-life and is rapidly degraded, it is proposed to exert wide-ranging pathophysiological actions. Whilst the precise nature of many of its effects is unclear, accumulating evidence supports positive actions on both metabolism and cardiovascular function. For example, obestatin has been reported to inhibit food and water intake, body weight gain and gastrointestinal motility and also to mediate promotion of cell survival and prevention of apoptosis. Obestatin-induced increases in beta cell mass, enhanced adipogenesis and improved lipid metabolism have been noted along with up-regulation of genes associated with beta cell regeneration, insulin production and adipogenesis. Furthermore, human circulating obestatin levels generally demonstrate an inverse association with obesity and diabetes, whilst the peptide has been shown to confer protective metabolic effects in experimental diabetes, suggesting that it may hold therapeutic potential in this setting. Obestatin also appears to be involved in blood pressure regulation and to exert beneficial effects on endothelial function, with experimental studies indicating that it may also promote cardioprotective actions against, for example, ischaemia-reperfusion injury. This review will present a critical appraisal of the expanding obestatin research area and discuss the emerging therapeutic potential of this peptide for both metabolic and cardiovascular complications of diabetes. AbbreviationsBK Ca , large conductance calcium-activated potassium channel; CART, cocaine-and amphetamine-related transcript; CCK, cholecystokinin; CRF, corticotrophin-releasing factor; GI, gastrointestinal; GLP-1, glucagon-like peptide-1; GLUT-4, glucose transporter type 4; HOMA-IR, homeostatic model assessment of insulin resistance; NPY, neuropeptide Y; PEG, polyethylene glycol; PI3K, phosphoinositide 3-kinase; POMC, proopiomelanocortin; SK6l, ribosomal protein s6 kinase; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; WAT, white adipose tissue.

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Obestatin Accelerates the Healing of Acetic Acid‐Induced Colitis in Rats

Cited by 36 publications

References 42 publications

Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

Exogenous Ghrelin Accelerates the Healing of Acetic Acid-Induced Colitis in Rats

Essential Role of Growth Hormone and IGF-1 in Therapeutic Effect of Ghrelin in the Course of Acetic Acid-Induced Colitis

Obestatin as a key regulator of metabolism and cardiovascular function with emerging therapeutic potential for diabetes

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