scholarly journals Anti-inflammatory and Anti-necrotic Effect of Lectins from Canavalia ensiformis and Canavalia brasiliensis in Experimental Acute Pancreatitis

2021 ◽  
Author(s):  
Samara Rodrigues Bonfim Damasceno Oliveira ◽  
Álvaro Xavier Franco ◽  
Marielle Pires Quaresma ◽  
Cecília Mendes Morais de Carvalho ◽  
Fabrícia da Cunha Jácome Marques ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Cell Death ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Cell Necrosis ◽  
Experimental Acute Pancreatitis ◽  
Canavalia Ensiformis ◽  
Acinar Cell Necrosis ◽  
Canavalia Brasiliensis

Abstract Lectins isolated from Canavalia ensiformis (ConA) and Canavalia brasiliensis (ConBr) are promising molecules to modulate cell death. Acute pancreatitis, characterized by acinar cell necrosis and inflammation, presents significant morbidity and mortality. This study has investigated the effects of ConA and ConBr on experimental acute pancreatitis and pancreatic acinar cell death induced by bile acid. Pancreatitis was induced by retrograde pancreatic ductal injection of 3% sodium taurocholate (Na-TC) in male Swiss mice. ConA or ConBr (0.1, 1 or 10 mg/kg) were intravenously applied to mice 1 h and 12 h after induction. After 24 hours, the severity of pancreatitis was evaluated by serum amylase and lipase, histopathological changes and myeloperoxidase assay. Pancreatic acinar cells were incubated with ConA (200 µg/ml) or ConBr (200 µg/ml) and taurolithocholic acid 3-sulfate (TLCS; 500 µM). Necrosis and changes in mitochondrial membrane potential (ΔѰm) were detected by fluorescence confocal microscopy. Treatment (post-insult) with ConA and ConBr decreased pancreatic damage caused by retrograde injection of Na-TC in mice, reducing pancreatic neutrophil infiltration, edema and necrosis. In addition, ConA and ConBr decreased pancreatic acinar cell necrosis and depolarization of ΔѰm caused by TLCS. The inhibition of necrosis was prevented by the lectin domain blockade; molecular docking analysis showed strong interaction of ConA and ConBr crystal structures with mannose residues. In conclusion, ConA and ConBr markedly inhibited in vitro and in vivo damage, effects partly dependent on the interaction with mannose residues on acinar cells. These data support the potential application of these proteins for treatment of acute pancreatitis.

373 Mechanisms Mediating Acinar Cell Necrosis and Autophagy in Experimental Acute Pancreatitis: the Role of PI3K Gamma

2009 ◽  
Vol 136 (5) ◽  
pp. A-61
Author(s):  
Wenzhuo Jia ◽  
Lars Fischer ◽  
Jae Hyuk Do ◽  
Sheyla Perez ◽  
Anna S. Gukovskaya ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acinar Cell ◽  
Cell Necrosis ◽  
Experimental Acute Pancreatitis ◽  
Pi3k Gamma ◽  
Acinar Cell Necrosis

Apoptosis versus necrosis in acute pancreatitis

2004 ◽  
Vol 286 (2) ◽  
pp. G189-G196 ◽  
Author(s):  
Madhav Bhatia
Keyword(s):  
Acute Pancreatitis ◽  
Cell Death ◽  
Acinar Cell ◽  
Cell Apoptosis ◽  
Cell Injury ◽  
Experimental Studies ◽  
Acinar Cells ◽  
Inflammatory Cells ◽  
Pancreatic Acinar Cell ◽  
Mild Acute Pancreatitis

Acute pancreatitis is a disease of variable severity in which some patients experience mild, self-limited attacks, whereas others manifest a severe, highly morbid, and frequently lethal attack. The events that regulate the severity of acute pancreatitis are, for the most part, unknown. It is generally believed that the earliest events in acute pancreatitis occur within acinar cells and result in acinar cell injury. Other processes, such as recruitment of inflammatory cells and generation of inflammatory mediators, are believed to occur subsequent to acinar cell injury, and these “downstream” events are believed to influence the severity of the disease. Several recently reported studies, however, have suggested that the acinar cell response to injury may, itself, be an important determinant of disease severity. In these studies, mild acute pancreatitis was found to be associated with extensive apoptotic acinar cell death, whereas severe acute pancreatitis was found to involve extensive acinar cell necrosis but very little acinar cell apoptosis. These observations led to the hypothesis that apoptosis could be a favorable response to acinar cells and that interventions that favor induction of apoptotic, as opposed to necrotic, acinar cell death might reduce the severity of an attack of acute pancreatitis. Indeed, in an experimental setting, the induction of pancreatic acinar cell apoptosis protects mice against acute pancreatitis. Little is known about the mechanism of apoptosis in the pancreatic acinar cell, although some early attempts have been made in that direction. Also, clinical relevance of these experimental studies remains to be investigated.

Chrm3 protects against acinar cell necrosis by stabilizing caspase‐8 expression in severe acute pancreatitis mice model

2019 ◽  
Vol 121 (3) ◽  
pp. 2618-2631 ◽  
Author(s):  
Ning Huang ◽  
Ghulam Murtaza ◽  
Lujing Wang ◽  
Jing Luan ◽  
Xinlei Wang ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Acinar Cell ◽  
Caspase 8 ◽  
Cell Necrosis ◽  
Mice Model ◽  
Acinar Cell Necrosis

scholarly journals MECOM permits pancreatic acinar cell dedifferentiation avoiding cell death under stress conditions

2020 ◽  
Author(s):  
Elyne Backx ◽  
Elke Wauters ◽  
Jonathan Baldan ◽  
Mathias Van Bulck ◽  
Ellis Michiels ◽  
...  
Keyword(s):  
Cell Death ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Stress Conditions ◽  
Loss Of Function ◽  
Cell Dedifferentiation ◽  
Duct Cells

ABSTRACTMaintenance of the pancreatic acinar cell phenotype suppresses tumor formation. Hence, repetitive acute or chronic pancreatitis, stress conditions in which the acinar cells dedifferentiate, predispose for cancer formation in the pancreas. Dedifferentiated acinar cells acquire a large panel of duct cell specific markers. However, it remains unclear to what extent dedifferentiated acini differ from native duct cells and which genes are uniquely regulating acinar cell dedifferentiation. Moreover, most studies have been performed in mouse since the availability of human cells is scarce.Here, we applied a non-genetic lineage tracing method in our culture model of human pancreatic exocrine cells that allowed cell-type specific gene expression profiling by RNA sequencing. Subsequent to this discovery analysis, one transcription factor that was unique for dedifferentiated acinar cells was functionally characterized using in vitro and in vivo genetic loss-of-function experimental models.RNA sequencing analysis showed that human dedifferentiated acinar cells expressed genes in ‘Pathways of cancer’ with prominence of the transcription factor MECOM (EVI-1) that was absent from duct cells. During mouse embryonic development, pre-acinar cells transiently expressed MECOM and MECOM was re-expressed in experimental in vivo models of acute and chronic pancreatitis in vivo, conditions in which acinar cells dedifferentiate. MECOM expression correlated with and was directly regulated by SOX9. MECOM loss-of-function in mouse acinar cells in vitro and in vivo impaired cell adhesion resulting in more prominent acinar cell death and suppressed acinar cell dedifferentiation by limiting ERK signaling.In conclusion, we transcriptionally profiled the two major human pancreatic exocrine cell types, acinar and duct cells, during experimental stress conditions. We provide insights that in dedifferentiated acinar cells, cancer pathways are upregulated in which MECOM is a critical regulator that suppresses acinar cell death by permitting cellular dedifferentiation.

Pancreatic acinar cell necrosis with intact storage of digestive enzymes in selenomethionine treated rats

1989 ◽  
Vol 58 (1) ◽  
pp. 397-403 ◽  
Author(s):  
Antti J. Hietaranta ◽  
Timo J. Nevalainen ◽  
Heikki J. Aho ◽  
Outi M. Hämäläinen ◽  
Sari H. Suortamo
Keyword(s):  
Acinar Cell ◽  
Digestive Enzymes ◽  
Pancreatic Acinar Cell ◽  
Cell Necrosis ◽  
Acinar Cell Necrosis

Substance P treatment stimulates chemokine synthesis in pancreatic acinar cells via the activation of NF-κB

2006 ◽  
Vol 291 (6) ◽  
pp. G1113-G1119 ◽  
Author(s):  
Raina Devi Ramnath ◽  
Madhav Bhatia
Keyword(s):  
Acute Pancreatitis ◽  
Substance P ◽  
Acinar Cell ◽  
Cell Injury ◽  
Acinar Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Chemokine Production ◽  
Pancreatic Acini ◽  
Monocyte Chemoattractant Protein 1

Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction and to the subsequent systemic inflammatory response, which may result in multiple organ dysfunction and death. Inflammatory mediators, including chemokines and substance P (SP), are known to play a crucial role in the pathogenesis of acute pancreatitis. It has been shown that pancreatic acinar cells produce the chemokine monocyte chemoattractant protein-1 (MCP-1) in response to caerulein hyperstimulation, demonstrating that acinar-derived MCP-1 is an early mediator of inflammation in acute pancreatitis. Similarly, SP levels in the pancreas and pancreatic acinar cell expression of neurokinin-1 receptor, the primary receptor for SP, are both increased during secretagogue-induced experimental pancreatitis. This study aims to examine the functional consequences of exposing mouse pancreatic acinar cells to SP and to determine whether it leads to proinflammatory signaling, such as production of chemokines. Exposure of mouse pancreatic acini to SP significantly increased synthesis of MCP-1, macrophage inflammatory protein-1α (MIP-1α), as well as MIP-2. Furthermore, SP also increased NF-κB activation. The stimulatory effect of SP was specific to chemokine synthesis through the NF-κB pathway, since the increase in chemokine production was completely attenuated when pancreatic acini were pretreated with the selective NF-κB inhibitor NF-κB essential modulator-binding domain peptide. This study shows that SP-induced chemokine synthesis in mouse pancreatic acinar cells is NF-κB dependent.

2′,4′,6′-Tris(methoxymethoxy) chalcone (TMMC) attenuates the severity of cerulein-induced acute pancreatitis and associated lung injury

2011 ◽  
Vol 301 (4) ◽  
pp. G694-G706 ◽  
Author(s):  
Tae-Hyeon Kim ◽  
Gi-Sang Bae ◽  
Hyo-Jeong Oh ◽  
Min-Sun Kim ◽  
Kyoung-Chel Park ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Cell Death ◽  
Lung Injury ◽  
Acinar Cell ◽  
Neutralizing Antibodies ◽  
Acinar Cells ◽  
Pancreatic Acinar Cells ◽  
Systemic Complications ◽  
Neutrophil Sequestration ◽  
Tnf Α

Acute pancreatitis (AP) is an inflammatory disease involving acinar cell injury and rapid production and release of inflammatory cytokines, which play a dominant role in local pancreatic inflammation and systemic complications. 2′,4′,6′-Tris (methoxymethoxy) chalcone (TMMC), a synthetic chalcone derivative, displays potent anti-inflammatory effects. Therefore, we aimed to investigate whether TMMC might affect the severity of AP and pancreatitis-associated lung injury in mice. We used the cerulein hyperstimulation model of AP. Severity of pancreatitis was determined in cerulein-injected mice by histological analysis and neutrophil sequestration. The pretreatment of mice with TMMC reduced the severity of AP and pancreatitis-associated lung injury and inhibited several biochemical parameters (activity of amylase, lipase, trypsin, trypsinogen, and myeloperoxidase and production of proinflammatory cytokines). In addition, TMMC inhibited pancreatic acinar cell death and production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 by inhibiting NF-κB and extracellular signal-regulated protein kinase 1/2 (ERK1/2) activation. Neutralizing antibodies for TNF-α, IL-1β, and IL-6 inhibited cerulein-induced cell death in isolated pancreatic acinar cells. Moreover, pharmacological blockade of NF-κB/ERK1/2 reduced acinar cell death and production of TNF-α, IL-1β, and IL-6 in isolated pancreatic acinar cells. In addition, posttreatment of mice with TMMC showed reduced severity of AP and lung injury. Our results suggest that TMMC may reduce the complications associated with pancreatitis.

NQDI-1 protects against acinar cell necrosis in three experimental mouse models of acute pancreatitis

2019 ◽  
Vol 520 (1) ◽  
pp. 211-217 ◽  
Author(s):  
Xiaochun Xie ◽  
Chenchen Yuan ◽  
Ling Yin ◽  
Qingtian Zhu ◽  
Nan Ma ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Mouse Models ◽  
Acinar Cell ◽  
Cell Necrosis ◽  
Experimental Mouse ◽  
Acinar Cell Necrosis

scholarly journals Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Guotao Lu ◽  
Zhihui Tong ◽  
Yanbing Ding ◽  
Jinjiao Liu ◽  
Yiyuan Pan ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Acinar Cell ◽  
Acinar Cells ◽  
Pancreatic Tissue ◽  
Pancreatic Acinar Cell ◽  
Cell Nuclei ◽  
Associated Proteins ◽  
Anti Inflammatory

Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP.

Sign in / Sign up

Export Citation Format

Share Document