scholarly journals Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yunan Wang ◽  
Abudurexiti Kayoumu ◽  
Guotao Lu ◽  
Pengfei Xu ◽  
Xu Qiu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Necrotizing Pancreatitis ◽  
Sodium Taurocholate ◽  
Concomitant Administration ◽  
Inflammatory Cells ◽  
Neutrophil Infiltration ◽  
Pancreatic Injury ◽  
Experimental Models ◽  
Myeloperoxidase Activity ◽  
Human Acute Pancreatitis

Abstract The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans.

scholarly journals Necroptosis protects against exacerbation of acute pancreatitis

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Michittra Boonchan ◽  
Hideki Arimochi ◽  
Kunihiro Otsuka ◽  
Tomoko Kobayashi ◽  
Hisanori Uehara ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Necrotizing Pancreatitis ◽  
Neutrophil Infiltration ◽  
Dependent Manner ◽  
Protective Effects ◽  
Interacting Protein ◽  
Inflammatory Conditions ◽  
Edematous Pancreatitis ◽  
Genetic Deletion ◽  
Dose Dependent

AbstractThe sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3−/− or Mlkl−/− mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3−/− mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl−/− mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl−/− mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.

scholarly journals Erratum: Corrigendum: Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yunan Wang ◽  
Abudurexiti Kayoumu ◽  
Guotao Lu ◽  
Pengfei Xu ◽  
Xu Qiu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Golden Hamster ◽  
Experimental Models ◽  
Syrian Golden Hamster ◽  
Human Acute Pancreatitis

scholarly journals Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis

2006 ◽  
Vol 290 (4) ◽  
pp. G772-G781 ◽  
Author(s):  
Shinya Ohashi ◽  
Akiyoshi Nishio ◽  
Hajime Nakamura ◽  
Masahiro Kido ◽  
Satoru Ueno ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Defense Mechanism ◽  
Intraperitoneal Administration ◽  
Neutrophil Infiltration ◽  
Myeloperoxidase Activity ◽  
Experimental Acute Pancreatitis ◽  
Redox Active ◽  
Thioredoxin 1 ◽  
Anti Inflammatory

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of κB-α, thereby suppressing proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.

Acute lung injury in two experimental models of acute pancreatitis: Infusion of saline or sodium taurocholate into the pancreatic duct

2000 ◽  
Vol 28 (5) ◽  
pp. 1497-1502 ◽  
Author(s):  
Arnaldo Lichtenstein ◽  
Rodolfo Milani ◽  
Sandra M. Fernezlian ◽  
Adriana S. Leme ◽  
Vera L. Capelozzi ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Pancreatic Duct ◽  
Sodium Taurocholate ◽  
Experimental Models

scholarly journals Adenovirus-mediated artificial miRNA targetting fibrinogen-like protein 2 attenuates the severity of acute pancreatitis in mice

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Xiaohua Ye ◽  
Jin Ding ◽  
Yanping Chen ◽  
Jiayue Dong
Keyword(s):  
Acute Pancreatitis ◽  
Western Blotting ◽  
Early Stage ◽  
Sodium Taurocholate ◽  
Pancreatic Injury ◽  
Protective Role ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Mrna Levels ◽  
Artificial Mirna ◽  
Tnf Α

Severe acute pancreatitis (SAP) remains to be challenging for its unpredictable inflammatory progression from acute pancreatitis to SAP. Apoptosis is an important pathology of SAP. Fibrinogen-like protein 2 (FGL2) has been reported to be involved in apoptosis. The present study aimed to explore the therapeutic effect of an adenovirus-mediated artificial miRNA targetting FGL2 (Ad-FGL2-miRNA) in taurocholate-induced murine pancreatitis models. Sodium taurocholate was retrogradely injected into the biliopancreatic ducts of the C57/BL mice to induce SAP. FGL2 expression was measured with reverse transcription-PCR, Western blotting, and immunohistochemical staining. ELISA was used to detect the activity of amylase and the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). In addition, the mRNA levels of TNF-α and IL-1β were also detected. Finally, apoptosis was assessed by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick-end labeling (TUNEL) method and Western blotting. Ad-FGL2-miRNA significantly suppressed FGL2 expression and alleviated pancreatic injury. Also, Ad-FGL2-miRNA markedly inhibited a post-SAP increase in the activation of TNF-α and IL-1β. Finally, pretreatment with Ad-FGL2-miRNA ameliorated apoptosis at the early stage of SAP by modulating cleaved caspase-3 and therefore played a protective role. These results indicated that FGL2 might be a promising target for attenuating the severity of SAP and adenovirus-mediated artificial miRNAs targetting FGL2 represented a potential therapeutic approach for the treatment of SAP.

scholarly journals Trimetazidine Increases Cell Survival and Inhibits the Activation of Inflammatory Response in Sodium Taurocholate–Induced Acute Pancreatitis

2017 ◽  
Vol 102 (11-12) ◽  
pp. 542-551
Author(s):  
Sevil Işık ◽  
Neriman Şengül ◽  
Fatma Töre ◽  
Cemalettin Aydın ◽  
Açelya Aslan ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Apoptotic Cell ◽  
Sodium Taurocholate ◽  
Specific Treatment ◽  
Antioxidant Enzyme Activities ◽  
Therapeutic Effects ◽  
Myeloperoxidase Activity ◽  
Cell Counts ◽  
Diphenyltetrazolium Bromide ◽  
Cytokine Levels

Objective: To evaluate the therapeutic effects of trimetazidine (TMZ) in an experimental acute pancreatitis (AP) model induced with sodium taurocholate (STC). Summary of Background Data: At present, AP is considered a disease with no specific treatment. Preventing mitochondrial dysfunction in acinar cells may be an option for specific treatment of AP. TMZ is an anti-ischemic drug with anti-inflammatory, antioxidant, and mitochondrial modulatory effects. Methods: Rats were divided into 4 groups. AP was induced in the AP (n = 7) and AP + TMZ (n = 7) groups by an injection of 4% sodium taurocholate to the pancreatic duct. The sham (n = 6) and drug (n = 6) groups were designated as control groups. The AP + TMZ and drug groups were administered TMZ. Samples were taken at 72 hours, and histopathologic changes as well as biochemical parameters were analyzed. Results: Serum amylase, tissue myeloperoxidase activity, malondialdehyde levels, serum cytokine levels, and mast cell degranulation rates were elevated after induction of AP, whereas tissue antioxidant enzyme activities and cell viability rates [determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay] decreased. These parameters were found to be different in the AP group compared with those in all other groups (P < 0.05). A significant improvement of all parameters was achieved with the TMZ treatment of AP. Histologically, significant differences were found between the AP and AP + TMZ groups in terms of leukocyte infiltration, necrosis, and apoptotic cell counts. Conclusions: In this study, we demonstrated that TMZ treatment protected the mitochondrial function and prevented the activation of the inflammatory cascade in the sodium taurocholate–induced AP model.

scholarly journals Extracellular release of ATP promotes systemic inflammation during acute pancreatitis

2019 ◽  
Vol 317 (4) ◽  
pp. G463-G475
Author(s):  
Ajay Dixit ◽  
Hassam Cheema ◽  
John George ◽  
Srikanth Iyer ◽  
Vikas Dudeja ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Systemic Inflammation ◽  
Purinergic Signaling ◽  
Lavage Fluid ◽  
Pancreatic Injury ◽  
P2 Receptors ◽  
Experimental Models ◽  
Lung Histology ◽  
Plasma Cytokines

In the current study, we explored the role of extracellular ATP (eATP) in promoting systemic inflammation during development of acute pancreatitis (AP). Release of extracellular (e)ATP was evaluated in plasma and bronchoalveolar lavage fluid (BALF) of mice with experimental acute pancreatitis (AP). Prophylactic intervention using apyrase or suramin was used to understand the role and contribution of eATP in pancreatitis-associated systemic injury. AP of varying severity was induced in C57BL/6 mice using 1-day or 2-day caerulein, caerulein + LPS and l-arginine models. eATP was measured in plasma and BALF. Mice were treated with suramin or apyrase in the caerulein and l-arginine models of AP. Plasma cytokines, lung, and pancreatic myeloperoxidase, and morphometric analysis of pancreatic and lung histology, were used to assess the severity of pancreatitis. Plasma eATP and purinergic 2 (P2) receptors in the pancreas and lungs were significantly elevated in the experimental models of AP. Blocking the effect of eATP by suramin led to reduced levels of plasma IL-6 and TNFα as well as reduced lung, and pancreatic injury. Neutralizing eATP with apyrase reduced systemic injury but did not ameliorate local injury. The results of this study support the role of eATP and P2 receptors in promoting systemic inflammation during AP. Modulating purinergic signaling during AP can be an important therapeutic strategy in controlling systemic inflammation and, thus, systemic inflammatory response syndrome during AP. NEW & NOTEWORTHY Released ATP from injured cells promotes systemic inflammation in acute pancreatitis

Rosmarinic Acid Attenuates Sodium Taurocholate-Induced Acute Pancreatitis in Rats by Inhibiting Nuclear Factor-κB Activation

2015 ◽  
Vol 43 (06) ◽  
pp. 1117-1135 ◽  
Author(s):  
Yu-Ting Fan ◽  
Guo-Jian Yin ◽  
Wen-Qin Xiao ◽  
Lei Qiu ◽  
Ge Yu ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Rosmarinic Acid ◽  
Interleukin 1 ◽  
Sodium Taurocholate ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Acinar Cells ◽  
Myeloperoxidase Activity ◽  
Tnf Α

Rosmarinic Acid (RA), a caffeic acid ester, has been shown to exert anti-inflammation, anti-oxidant and antiallergic effects. Our study aimed to investigate the effect of RA in sodium taurocholate ( NaTC )-induced acute pancreatitis, both in vivo and in vitro. In vivo, RA (50 mg/kg) was administered intraperitoneally 2 h before sodium taurocholate injection. Rats were sacrificed 12 h, 24 h or 48 h after sodium taurocholate injection. Pretreatment with RA significantly ameliorated pancreas histopathological changes, decreased amylase and lipase activities in serum, lowered myeloperoxidase activity in the pancreas, reduced systematic and pancreatic interleukin-1 β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and inhibited NF-κB translocation in pancreas. In vitro, pretreating the fresh rat pancreatic acinar cells with 80 μ mol/L RA 2 h before 3750 nmol/L sodium taurocholate or 10 ng/L TNF-α administration significantly attenuated the reduction of isolated pancreatic acinar cell viability and inhibited the nuclear activation and translocation of NF-κB. Based on our findings, RA appears to attenuate damage in sodium taurocholate-induced acute pancreatitis and reduce the release of inflammatory cytokines by inhibiting the activation of NF-κB. These findings might provide a basis for investigating the therapeutic role of RA in managing acute pancreatits.

scholarly journals Kaempferol protects rats with severe acute pancreatitis through regulating NF-κB and Keap1–Nrf2 signaling pathway

2021 ◽  
Vol 33 (3) ◽  
pp. 25-32
Author(s):  
Jun Cai ◽  
Suyan Yao ◽  
Hao Wang ◽  
Wei Rong
Keyword(s):  
Acute Pancreatitis ◽  
Signaling Pathway ◽  
Severe Acute Pancreatitis ◽  
Sodium Taurocholate ◽  
Pancreatic Injury ◽  
Related Factor ◽  
Inflammatory Disorder ◽  
Nuclear Factor ◽  
Western Blot Assay ◽  
Nrf2 Signaling Pathway

Kaempferol (KF) is an important natural anti-inflammatory flavonol. Acute pancreatitis (AP) is an inflammatory disorder, which in about 20% cases may develop into severe acute pancreatitis (SAP) with a high mortality rate. This research was to study the effects and mechanism of kaempferol on SAP. SAP was induced by sodium taurocholate. The level of cytokines was analyzed by enzyme-linked-immunosorbent serologic assay. The expression of nuclear factor kappa B (NF-κB) and Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2 (Keap1–Nrf2) proteins was analyzed by Western blot assay. Pathological changes in the pancreas were evaluated by hematoxylin and eosin staining. Kaempferol attenuated pancreatic injury in SAP rats, including reduction in inflammatory infiltration and necrosis. The level of serum amylase and lipase was also decreased in kaempferol-treated SAP rats. Kaempferol inhibited the expression of inflammatory mediators (nuclear factor-α, Interlukin-1β, and Interlukin-6), and alleviated the oxidative stress characterized by the decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD) levels. Kaempferol decreased the expression of cleaved caspase 3 and anti-apoptotic protein Bcl-2, which indicated that kaempferol could inhibit apoptosis of pancreatic cells in SAP rats. Kaempferol treatment could decrease the expression of p-p65 and the amount of nuclear Nrf2 (Nu-Nrf2), which demonstrated that kaempferol inhibited the NF-κB activation and enhanced the Keap1–Nrf2 pathway. Our research indicated that kaempferol could attenuate the pancreatic injury of SAP by regulating NF-κB and Keap1–Nrf2 signaling pathway. Kaempferol could serve as a natural candidate for treating SAP.

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