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Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

Bukowczan J, Warzecha Z, Ceranowicz P, Kuśnierz-Cabala B, Tomaszewska R - PLoS ONE (2015)

Bottom Line: Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain.Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow.The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Diabetes Mellitus, Northumbria NHS Foundation Trust, Rake Lane, North Shields, Tyne and Wear, United Kingdom.

ABSTRACT

Objective: Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.

Aim: The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.

Methods: Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.

Results: Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and pancreatic exocrine secretion. Administration of obestatin at doses used was without significant effect with regard to daily food intake or pancreatic exocrine secretion in sham-operated rats, as well as in rats with acute pancreatitis. On the other hand, obestatin abolished a statistical significance of difference in food intake between animals with AP and control animals without pancreatic fistula and induction of AP.

Conclusion: Treatment with the exogenous obestatin reduces severity of ischemia/reperfusion-induced acute pancreatitis and accelerates recovery in this disease. The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.

No MeSH data available.


Related in: MedlinePlus

Representative morphological features of the pancreas.Hematoxilin-eosin counterstain. Histological images are presented in two different magnification for each group. In left column, original magnification 100×. In right column, original magnification 200×. (panel A) sham-operated control rats treated with saline; (panel B) rats with ischemia/reperfusion-induced pancreatitis after 1-day reperfusion; (panel C) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with saline; (panel D) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with obestatin; (panel E) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with saline; (panel F) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with obestatin; (panel G) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with saline; (panel H) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with obestatin; (panel I) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with saline; (panel J) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with obestatin. Saline or obestatin (8 nmol/kg/dose) were given i.p. twice a day, starting 24 h after induction of acute pancreatitis.
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pone.0134380.g006: Representative morphological features of the pancreas.Hematoxilin-eosin counterstain. Histological images are presented in two different magnification for each group. In left column, original magnification 100×. In right column, original magnification 200×. (panel A) sham-operated control rats treated with saline; (panel B) rats with ischemia/reperfusion-induced pancreatitis after 1-day reperfusion; (panel C) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with saline; (panel D) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with obestatin; (panel E) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with saline; (panel F) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with obestatin; (panel G) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with saline; (panel H) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with obestatin; (panel I) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with saline; (panel J) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with obestatin. Saline or obestatin (8 nmol/kg/dose) were given i.p. twice a day, starting 24 h after induction of acute pancreatitis.

Mentions: Histological scoring of pancreatic tissue damage in rats with or without ischemia/reperfusion-induced AP, and treated with either saline or obestatin is presented in Table 1. Pancreatic ischemia followed by reperfusion induced acute hemorrhagic pancreatitis in all tested animals. Twenty four hours after the beginning of reperfusion, at the light microscopic level, moderate inter- and intralobular edema was accompanied by moderate perivascular and scarce diffuse leukocyte infiltrations of the pancreatic tissue. Vacuolization was present in less than 25% of acinar cells. Necrosis involved less than 15–35% of pancreatic cells. In addition, 1–5 hemorrhagic foci per slide were observed in rats with AP (Table 1; Fig 6B). During the course of disease, the histological signs of tissue damage were spontaneously reduced and only interlobular edema, mild perivascular leukocyte infiltrations, and vacuolization present in less than 25% of acinar cells were observed at the 14th day of pancreatic reperfusion (Table 1; Fig 6E, 6G and 6I). Treatment with obestatin accelerated pancreatic regeneration, and no microscopic signs of pancreatic injury, except the presence of mild perivascular leukocyte infiltrations, were observed in animals treated with the polypeptide at the last day of the experiment (Table 1, Fig 6J).


Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

Bukowczan J, Warzecha Z, Ceranowicz P, Kuśnierz-Cabala B, Tomaszewska R - PLoS ONE (2015)

Representative morphological features of the pancreas.Hematoxilin-eosin counterstain. Histological images are presented in two different magnification for each group. In left column, original magnification 100×. In right column, original magnification 200×. (panel A) sham-operated control rats treated with saline; (panel B) rats with ischemia/reperfusion-induced pancreatitis after 1-day reperfusion; (panel C) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with saline; (panel D) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with obestatin; (panel E) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with saline; (panel F) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with obestatin; (panel G) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with saline; (panel H) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with obestatin; (panel I) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with saline; (panel J) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with obestatin. Saline or obestatin (8 nmol/kg/dose) were given i.p. twice a day, starting 24 h after induction of acute pancreatitis.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4520493&req=5

pone.0134380.g006: Representative morphological features of the pancreas.Hematoxilin-eosin counterstain. Histological images are presented in two different magnification for each group. In left column, original magnification 100×. In right column, original magnification 200×. (panel A) sham-operated control rats treated with saline; (panel B) rats with ischemia/reperfusion-induced pancreatitis after 1-day reperfusion; (panel C) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with saline; (panel D) rats with ischemia/reperfusion-induced pancreatitis after 2-days reperfusion and treated with obestatin; (panel E) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with saline; (panel F) rats with ischemia/reperfusion-induced pancreatitis after 5-days reperfusion and treated with obestatin; (panel G) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with saline; (panel H) rats with ischemia/reperfusion-induced pancreatitis after 9-days reperfusion and treated with obestatin; (panel I) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with saline; (panel J) rats with ischemia/reperfusion-induced pancreatitis after 14-days reperfusion and treated with obestatin. Saline or obestatin (8 nmol/kg/dose) were given i.p. twice a day, starting 24 h after induction of acute pancreatitis.
Mentions: Histological scoring of pancreatic tissue damage in rats with or without ischemia/reperfusion-induced AP, and treated with either saline or obestatin is presented in Table 1. Pancreatic ischemia followed by reperfusion induced acute hemorrhagic pancreatitis in all tested animals. Twenty four hours after the beginning of reperfusion, at the light microscopic level, moderate inter- and intralobular edema was accompanied by moderate perivascular and scarce diffuse leukocyte infiltrations of the pancreatic tissue. Vacuolization was present in less than 25% of acinar cells. Necrosis involved less than 15–35% of pancreatic cells. In addition, 1–5 hemorrhagic foci per slide were observed in rats with AP (Table 1; Fig 6B). During the course of disease, the histological signs of tissue damage were spontaneously reduced and only interlobular edema, mild perivascular leukocyte infiltrations, and vacuolization present in less than 25% of acinar cells were observed at the 14th day of pancreatic reperfusion (Table 1; Fig 6E, 6G and 6I). Treatment with obestatin accelerated pancreatic regeneration, and no microscopic signs of pancreatic injury, except the presence of mild perivascular leukocyte infiltrations, were observed in animals treated with the polypeptide at the last day of the experiment (Table 1, Fig 6J).

Bottom Line: Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain.Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow.The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Diabetes Mellitus, Northumbria NHS Foundation Trust, Rake Lane, North Shields, Tyne and Wear, United Kingdom.

ABSTRACT

Objective: Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.

Aim: The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.

Methods: Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose) was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.

Results: Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and pancreatic exocrine secretion. Administration of obestatin at doses used was without significant effect with regard to daily food intake or pancreatic exocrine secretion in sham-operated rats, as well as in rats with acute pancreatitis. On the other hand, obestatin abolished a statistical significance of difference in food intake between animals with AP and control animals without pancreatic fistula and induction of AP.

Conclusion: Treatment with the exogenous obestatin reduces severity of ischemia/reperfusion-induced acute pancreatitis and accelerates recovery in this disease. The involved mechanisms are likely to be multifactorial, and are mediated, at least in part, by anti-inflammatory properties of obestatin.

No MeSH data available.


Related in: MedlinePlus