Platelet-Activating Factor Mediates Pancreatic Function Derangement in Caerulein-Induced Pancreatitis in Rats

1994 ◽  
Vol 87 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Ricardo Alonso ◽  
Angel Montero ◽  
Miguel Arévalo ◽  
Luis J. García ◽  
Concepción Sánchez-Vicente ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Platelet Activating Factor ◽  
Blood Platelet ◽  
Pancreatic Tissue ◽  
Portal Blood ◽  
Blood Levels ◽  
Inflammatory Infiltration ◽  
Subcutaneous Injections ◽  
Protein Output

1. We have assessed the role of platelet-activating factor in caerulein-induced acute pancreatitis (four subcutaneous injections of caerulein at a dose of 20 μg/kg) by measuring platelet-activating factor levels in portal blood, pancreatic tissue and peritoneal exudate in rats with and without pancreatitis. 2. We have also observed the effect of the platelet-activating factor antagonist, BN-52021, on the hyper-amylasaemia and exocrine pancreatic secretion impairment associated with pancreatitis. 3. In rats with pancreatitis the basal pancreatic flow rate was increased (1.63 ± 0.41 versus 0.25 ± 0.03 μl/min). Total protein output was similar in both untreated (5.98 ± 1.93 μg/min) and caerulein-injected (6.5 ± 2.0 μg/min) animals. Amylase output was lower in rats with pancreatitis (19.6 ± 4.8 μ-units/min) than in controls (39.4 ± 16.6 μ-units/min). 4. Caerulein-treated animals had significantly higher serum amylase levels than untreated animals. BN-52021 significantly reduced the caerulein-induced hyperamylasaemia. 5. Portal blood platelet-activating factor levels increased in rats with pancreatitis and in rats infused with cholecystokinin. Rats injected with caerulein and BN-52021 had portal blood levels of platelet-activating factor that were lower than those with pancreatitis. 6. Morphological derangements associated with pancreatitis (inflammatory infiltration and cell vacuolization) were also markedly reduced in BN-52021-treated animals. 7. The results of this study suggest that platelet-activating factor is involved in the development of caerulein-induced acute pancreatitis in rats.

scholarly journals Impairment of PGC-1 Alpha Up-Regulation Enhances Nitrosative Stress in the Liver during Acute Pancreatitis in Obese Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 887
Author(s):  
Sergio Rius-Pérez ◽  
Isabel Torres-Cuevas ◽  
María Monsalve ◽  
Francisco J. Miranda ◽  
Salvador Pérez
Keyword(s):  
Acute Pancreatitis ◽  
Nitrosative Stress ◽  
Energy Charge ◽  
Pancreatic Tissue ◽  
Obese Mice ◽  
Antioxidant Genes ◽  
Regulated Expression ◽  
Distant Organ ◽  
Nos2 Expression

Acute pancreatitis is an inflammatory process of the pancreatic tissue that often leads to distant organ dysfunction. Although liver injury is uncommon in acute pancreatitis, obesity is a risk factor for the development of hepatic complications. The aim of this work was to evaluate the role of PGC-1α in inflammatory response regulation in the liver and its contribution to the detrimental effect of obesity on the liver during acute pancreatitis. For this purpose, we induced acute pancreatitis by cerulein in not only wild-type (WT) and PGC-1α knockout (KO) mice, but also in lean and obese mice. PGC-1α levels were up-regulated in the mice livers with pancreatitis. The increased PGC-1α levels were bound to p65 to restrain its transcriptional activity toward Nos2. Lack of PGC-1α favored the assembly of the p65/phospho-STAT3 complex, which promoted Nos2 expression during acute pancreatitis. The increased transcript Nos2 levels and the pro-oxidant liver status caused by the down-regulated expression of the PGC-1α-dependent antioxidant genes enhanced nitrosative stress and decreased energy charge in the livers of the PGC-1α KO mice with pancreatitis. It is noteworthy that the PGC-1α levels lowered in the obese mice livers, which increased the Nos2 mRNA expression and protein nitration levels and decreased energy charge during pancreatitis. In conclusion, obesity impairs PGC-1α up-regulation in the liver to cause nitrosative stress during acute pancreatitis.

The Effect of Exocrine Pancreas Stimulation on the Coagulation and Fibrinolytic System in Dogs

1973 ◽  
Vol 29 (03) ◽  
pp. 603-609
Author(s):  
A Gabryelewicz ◽  
J Prokopowicz ◽  
W Szalaj ◽  
N Wolosowicz ◽  
W Laszewicz ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Prothrombin Time ◽  
Fibrinolytic Activity ◽  
Exocrine Pancreas ◽  
Blood Platelet ◽  
Fibrinolytic System

SummaryThe coagulation and fibrinolytic systems have been investigated in the dogs treated intravenously with secretin, pancreozymin and CCK.There was significant shortening of plastic and glass clotting times, a fall in blood platelet numbers, prolongation of the prothrombin time, and a transitory inhibition of plasma euglobulin fibrinolytic activity. The greatest changes were found after CCK.It should be stressed that the peak changes were earlier and more intense when morphine was given with the hormones.In the authors’ opinion the present findings support the supposition concerning the role of enzymatic toxemia in hemostatic disturbances seen in acute pancreatitis.

scholarly journals The Role of TLR-4 and Galectin-3 Interaction in Acute Pancreatitis

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Milica Dimitrijevic Stojanovic ◽  
Bojan Stojanovic ◽  
Nebojsa Arsenijevic ◽  
Bojana Stojanovic
Keyword(s):  
Acute Pancreatitis ◽  
Immune Cells ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Innate Immune ◽  
Type I ◽  
Innate Immune Cells ◽  
Enhanced Production ◽  
Galectin 3

AbstractToll-like receptor-4 (TLR-4) is a member of evolutionarily conserved type I transmembrane proteins that can initiate sterile inflammatory cascade in the pancreas. Expression of TLR-4 is up-regulated in pancreatic tissue, as well as, on peripheral blood innate immune cells in human and experimental models of acute pancreatitis. TLR-4 plays important pro-inflammatory roles during development of acute pancreatitis: it recognize alarmins released from injured acinar cells and promotes activation and infiltration of innate immune cells after the premature and intraacinar activation of tripsinogen. Galectin-3 is β-galactoside-binding lectin that plays pro-inflammatory roles in a variety autoimmune diseases, acute bacterial infections and during tumorigenesis. It is reported that Galectin-3 is alarmin in experimental models of neuroinflammation and binds to TLR-4 promoting the pro-inflammatory phenotype of microglia. Also, in experimental model of acute pancreatitis Galectin-3 is colocalized with TLR-4 on innate inflammatory cells resulted in enhanced production of inflammatory cytokines, TNF-α and IL-1β, increased infiltration of pro-inflammatory N1 neutrophils, macrophages and dendritic cells and increased damage of pancreatic tissue. This review paper discusses the role of TLR-4/Gal-3 axis in the pathogenesis of acute pancreatitis.

scholarly journals Protective Effects of Rhubarb in Rats with Acute Pancreatitis and the Role of Its Active Compound Rhein on Mitochondria of Exocrine Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Jianlei Zhao ◽  
George Li ◽  
Wenbi Xiong ◽  
Litao Liu ◽  
Jin Xiang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Active Compound ◽  
Stellate Cell ◽  
Blood Perfusion ◽  
Pancreatic Tissue ◽  
Protective Effects ◽  
Mtor Signaling Pathway ◽  
Activity Inhibition ◽  
Potential Link

Da-Cheng-Qi-Decoction (DCQD) has been used in the treatment of acute pancreatitis (AP) in China for many years. The aim of the current study was to examine the principal ingredient rhubarb of DCQD and its potential link to the pancreatic repair effects in rats with AP. The pancreatitis was induced in SD rats by intraperitoneal injections of cerulein. The results showed that rhubarb significantly increased blood perfusion of pancreatic tissue, reversed mitochondrial damage, and promoted pancreatic acinar and stellate cell proliferation. In addition, the rhein (from rhubarb) had high distribution in pancreas tissue and protected mitochondria in AR42J cells via the activation of PI3K/AKT/mTOR signaling pathway and activity inhibition of AMPK (P < 0.05). The results provide some preclinical evidence on the protective effects of DCQD for the treatment of acute pancreatitis. Rhein is regarded to be the active compound of rhubarb and can be expected to be a new compound for the treatment of AP.

scholarly journals Role of platelet activating factor in pathogenesis of acute pancreatitis in rats.

Gut ◽  
1992 ◽  
Vol 33 (9) ◽  
pp. 1268-1274 ◽  
Author(s):  
S J Konturek ◽  
A Dembinski ◽  
P J Konturek ◽  
Z Warzecha ◽  
J Jaworek ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Platelet Activating Factor

scholarly journals Dexmedetomidine reduces inflammation in mice with acute pancreatitis by inhibiting NLRP3 inflammasome and sympathetic nerve activity

2020 ◽  
Vol 19 (5) ◽  
pp. 943-947
Author(s):  
Yanjun Gao ◽  
JinHui Xie ◽  
Ruobin Liu ◽  
Yue Li ◽  
Wenjun Yan
Keyword(s):  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Nlrp3 Inflammasome ◽  
Sympathetic Nerve ◽  
Pancreatic Tissue ◽  
Inflammatory Factors ◽  
Blood Levels ◽  
Related Factors ◽  
Tnf Α ◽  
Net Protein

Purpose: To study the anti-inflammatory influence of dexmedetomidine (DEX) in mice with acute pancreatitis (AP), and to determine the underlying mechanism.Methods: A total of 75 healthy ICR male mice were randomly divided into control, mild acute pancreatitis (MAP), MAP+DEX, severe acute pancreatitis (SAP), and SAP+DEX groups, with 15 mice/group. Blood levels of inflammatory factors (TNF-α and IL-1β) and norepinephrine were assayed ineach group. Western blotting was used to assay the protein expressions of NLRP3 and norepinephrine transporter (NET) in the pancreatic tissue of each group.Results: The levels of inflammatory factors in the MAP+DEX group were markedly lower than those in the MAP group after 10 h of MAP induction (p < 0.01). Mice in MAP+DEX group had significantly lower expression of NLRP3 in pancreatic tissue, and significantly higher NET protein level, relative to the MAP mice. Following 10 h of SAP, concentrations of the inflammatory factors and the pancreatic expression of NLRP3 were lower in SAP+DEX-treated mice than in SAP mice, while NET protein was significantly higher in SAP mice (p < 0.01).Conclusion: DEX reduces the expressions of inflammation-related factors TNF-α and IL-1β, and inhibits inflammatory response in mice with AP via downregulation of NET protein expression via inhibition of NLRP3 and early sympathetic events. Keywords: Dexmedetomidine, NLRP3 inflammasome, Sympathetic nerve, Acute pancreatitis, Inflammatory response

scholarly journals Role of Interleukin-17 in Acute Pancreatitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Guanqun Li ◽  
Hongze Chen ◽  
Liwei Liu ◽  
Peng Xiao ◽  
Yu Xie ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Poor Prognosis ◽  
Acinar Cells ◽  
Therapeutic Strategies ◽  
Pancreatic Tissue ◽  
Vital Role ◽  
Interleukin 17 ◽  
Systemic Manifestations ◽  
Pathogenic Process

Acute pancreatitis (AP) is a leading cause of death and is commonly accompanied by systemic manifestations that are generally associated with a poor prognosis. Many cytokines contribute to pancreatic tissue damage and cause systemic injury. Interleukin-17 (IL-17) is a cytokine that may play a vital role in AP. Specifically, IL-17 has important effects on the immune response and causes interactions between different inflammatory mediators in the AP-related microenvironment. In this literature review, we will discuss the existing academic understanding of IL-17 and the impacts of IL-17 in different cells (especially in acinar cells and immune system cells) in AP pathogenesis. The clinical significance and potential mechanisms of IL-17 on AP deterioration are emphasized. The evidence suggests that inhibiting the IL-17 cytokine family could alleviate the pathogenic process of AP, and we highlight therapeutic strategies that directly or indirectly target IL-17 cytokines in acute pancreatitis.

scholarly journals Influence of calcitonin gene-related peptide on model mice with acute pancreatitis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jianxiong Hu ◽  
Yanya Lin ◽  
Shijun Chen ◽  
Yangfang Cai ◽  
Zhiwei Chen ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Blood Flow ◽  
B Lymphocytes ◽  
Intraperitoneal Injection ◽  
Calcitonin Gene Related Peptide ◽  
Pancreatic Tissue ◽  
Pancreatic Acinar Cells ◽  
Inflammatory Infiltration ◽  
Related Peptide ◽  
Calcitonin Gene

Abstract Objectives To establish model mice with acute pancreatitis (AP) and study influence of calcitonin gene-related peptide (CGRP) on AP. Methods The model mice with AP were firstly established by intraperitoneal injection of successive six doses of caerulein (100 μg/kg) and one dose of lipopolysaccharide (10 mg/kg). The intraperitoneal injection of CGRP (100 μg/kg) was performed to investigate influence of CGRP on AP, mainly involving the determination of amylase activity and the expression of CGRP and CD20+ B lymphocytes. Results CGRP on mice with AP could significantly reduce the severity of pancreatic pathological injury, the activity of amylase and the expression of CD20+ B lymphocytes. CGRP was significantly expressed in pancreatic tissue with AP, but CGRP receptor antagonist down-regulated the expression of CGRP and increased the number of CD20+ B lymphocytes, confirming the protective effect of CGRP on pancreatic tissue. Conclusions We preliminarily conclude that CGRP could significantly improve the pancreatic lesions and inflammatory infiltration of pancreas in mice with AP, and reduce the damage of pancreatic acinar cells, by mainly increasing blood flow and blood flow velocity of pancreas to improve the pancreatic microcirculation and effectively reducing the permeability of the microvessels to decrease the pathological damage degree of AP.

scholarly journals Qingyi decoction attenuates severe acute pancreatitis in rats via inhibition of inflammation and protection of the intestinal barrier

2019 ◽  
Vol 47 (5) ◽  
pp. 2215-2227 ◽  
Author(s):  
Song Su ◽  
Tiancheng Liang ◽  
Xiang Zhou ◽  
Kai He ◽  
Bo Li ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Intestinal Barrier ◽  
Pancreatic Tissue ◽  
Small Intestinal Mucosa ◽  
Barrier Dysfunction ◽  
Ileal Mucosa ◽  
Inflammatory Infiltration ◽  
Tnf Α

Objective Qingyi decoction (QYD) has beneficial effects in severe acute pancreatitis (SAP). We assessed the therapeutic effect and mechanisms of QYD in SAP. Methods A rat model of SAP was induced by pancreatic ductal injection of sodium taurocholate. QYD was administered intragastrically immediately postoperatively and once every 12 hours. Serum amylase, endotoxin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and D-lactate levels were measured at 12, 24, and 48 hours. Histological changes in the pancreas and ileum were analyzed. Expression of nuclear factor kappa-light-chain-enhancer of activated B cells p65 (NF-κB p65), Toll-like receptor 4 (TLR4), and zonula occludens-1 (ZO-1) in the small intestinal mucosa was also assessed. Results Pancreatic tissue showed extracellular space expansion, inflammatory infiltration, vessels with necrotic walls, and hemorrhage. Ileal tissue showed hemorrhage, inflammatory infiltration, and ileal mucosa destruction. These histological features were dramatically improved by QYD. Increased serum levels of amylase, endotoxin, TNF-α, IL-6, and D-lactic acid were significantly decreased by QYD administration. Increased expression of NF-κB p65 and TLR4 and decreased expression of ZO-1 in the ileal mucosa were also restored to normal levels by QYD treatment. Conclusion QYD alleviates SAP by reducing intestinal barrier dysfunction, inhibiting intestinal bacteria and endotoxin translocation, and preventing NF-κB activation.

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