Chaiqin Chengqi Decoction decreases pancreatic acinar cell calcium overload in rats with acute pancreatitis

Mechanisms leading to acute pancreatitis after a fat-enriched meal combined with excess alcohol are incompletely understood. We have studied the effects of alcohol and fat (VLDL) on pancreatic acinar cell (PAC) function, oxidative stress, and repair mechanisms by pancreatic stellate cells (PSC) leading to fibrogenesis. To do so, PAC (rat) were isolated and cultured up to 24 h. Ethanol and/or VLDL were added to PAC. We measured PAC function (amylase, lipase), injury (lactic dehydrogenase), apoptosis (TUNEL, Apo2.7, annexin V binding), oxidative stress, and lipid peroxidation (conjugated dienes, malondialdehyde, chemoluminescence); we also measured PSC proliferation (bromodeoxyuridine incorporation), matrix synthesis (immunofluorescence of collagens and fibronectin, fibronectin immunoassay), and fatty acids in PAC supernatants (gas chromatography). Within 6 h, cultured PAC degraded and hydrolyzed VLDL completely. VLDL alone (50 μg/ml) and in combination with alcohol (0.2, 0.5, and 1% vol/vol) induced PAC injury (LDL, amylase, and lipase release) within 2 h through generation of oxidative stress. Depending on the dose of VLDL and alcohol, apoptosis and/or necrosis were induced. Antioxidants (Trolox, Probucol) reduced the cytotoxic effect of alcohol and VLDL. Supernatants of alcohol/VLDL-treated PAC stimulated stellate cell proliferation and extracellular matrix synthesis. We concluded that, in the presence of lipoproteins, alcohol induces acinar cell injury. Our results provide a biochemical pathway for the clinical observation that a fat-enriched meal combined with excess alcohol consumption can induce acinar cell injury (acute pancreatitis) followed by repair mechanisms (proliferation and increased matrix synthesis in PSC).

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

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00177.2006 ◽

2006 ◽

Vol 291 (6) ◽

pp. G1113-G1119 ◽

Cited By ~ 34

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.

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Effect of long-term CCK blockade on the pancreatic acinar cell renewal in rats with acute pancreatitis

Peptides ◽

10.1016/s0196-9781(03)00112-8 ◽

2003 ◽

Vol 24 (4) ◽

pp. 535-541 ◽

Cited By ~ 1

Author(s):

Ana M de la Mano ◽

Sara Sevillano ◽

Manuel A Manso ◽

Isabel de Dios

Keyword(s):

Acute Pancreatitis ◽

Acinar Cell ◽

Pancreatic Acinar Cell ◽

Cell Renewal

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

BioMed Research International ◽

10.1155/2016/6089430 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 11

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.

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

10.21203/rs.3.rs-172690/v1 ◽

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.

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Inflammatory Response on the Pancreatic Acinar Cell Injury

Scandinavian Journal of Surgery ◽

10.1177/145749690509400203 ◽

2005 ◽

Vol 94 (2) ◽

pp. 97-102 ◽

Cited By ~ 62

Author(s):

M. Bhatia

Keyword(s):

Acute Pancreatitis ◽

Inflammatory Response ◽

Acinar Cell ◽

Cell Injury ◽

Critical Role ◽

Organ Damage ◽

Multiple Organ ◽

Pancreatic Acinar Cell ◽

Inflammatory Disorder ◽

Distant Organ

Acute pancreatitis is an inflammatory disorder, and inflammation not only affects the pathogenesis but also the course of the disease. Acinar cell injury early in acute pancreatitis leads to a local inflammatory reaction; if marked this leads to a systemic inflammatory response syndrome (SIRS). An excessive SIRS leads to distant organ damage and multiple organ dysfunction syndrome (MODS). MODS associated with acute pancreatitis is the primary cause of morbidity and mortality in this condition. Recent studies by us and other investigators have established the critical role played by inflammatory mediators such as TNF-α, IL-1β, IL-6, IL-8, CINC/GRO-α, MCP-1, PAF, IL-10, CD40L, C5a, ICAM-1, MIP1-α, RANTES, substance P, and hydrogen sulfide in acute pancreatitis and the resultant MODS. This review intends to present an overview of the inflammatory response that takes place following pancreatic acinar cell injury.

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