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 Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Xinnong Liu ◽  
Qingtian Zhu ◽  
Min Zhang ◽  
Tao Yin ◽  
Rong Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Tissue Injury ◽  
Pancreatic Tissue ◽  
Zinc Protoporphyrin ◽  
Dependent Manner ◽  
Protective Effects ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Flavonoid Monomer

Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.

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.

scholarly journals Progranulin attenuates liver fibrosis by downregulating the inflammatory response

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Wonbeak Yoo ◽  
Jaemin Lee ◽  
Kyung Hee Noh ◽  
Sangmin Lee ◽  
Dana Jung ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Raw 264.7 Cells ◽  
Protective Effects ◽  
Deficient Diet ◽  
A Cell

Abstract Progranulin (PGRN) is a cysteine-rich secreted protein expressed in endothelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being implicated in tissue remodeling, development, inflammation, and protein homeostasis. However, these findings are controversial, and the role of PGRN in liver disease remains unknown. In the current study, we examined the effect of PGRN in two different models of chronic liver disease, methionine‐choline‐deficient diet (MCD)-induced non-alcoholic steatohepatitis (NASH) and carbon tetrachloride (CCl4)-induced liver fibrosis. To induce long-term expression of PGRN, PGRN-expressing adenovirus was delivered via injection into the tibialis anterior. In the CCl4-induced fibrosis model, PGRN showed protective effects against hepatic injury, inflammation, and fibrosis via inhibition of nuclear transcription factor kappa B (NF-κB) phosphorylation. PGRN also decreased lipid accumulation and inhibited pro-inflammatory cytokine production and fibrosis in the MCD-induced NASH model. In vitro treatment of primary macrophages and Raw 264.7 cells with conditioned media from hepatocytes pre-treated with PGRN prior to stimulation with tumor necrosis factor (TNF)-α or palmitate decreased their expression of pro-inflammatory genes. Furthermore, PGRN suppressed inflammatory and fibrotic gene expression in a cell culture model of hepatocyte injury and primary stellate cell activation. These observations increase our understanding of the role of PGRN in liver injury and suggest PGRN delivery as a potential therapeutic strategy in chronic inflammatory liver disease.

Protective effect of Fragarria ananassa and Vaccinium corymbosum fruit extracts against L-arginine induced acute pancreatitis in rats

2019 ◽  
Author(s):  
Siva Reddy Challa ◽  
Veena Gadicherla ◽  
Mandava V. Basaveswara Rao ◽  
P. Ramakrishna ◽  
K.Pavan Kumar
Keyword(s):  
Acute Pancreatitis ◽  
Protective Effect ◽  
Dna Fragmentation ◽  
Antioxidant Properties ◽  
Vaccinium Corymbosum ◽  
Pancreatic Tissue ◽  
Protective Effects ◽  
Tissue Samples ◽  
Fruit Extracts ◽  
Histopathological Studies

The study was aimed to evaluate the protective effects of alcoholic extracts of Strawberry and Blueberry fruits [AESF and AEBF] in acute pancreatitis in rats. Treatment groups received AESF and AEBF at doses of 200 and 400 mg/kg for 7 days with prior injections of L-arginine on 5th day. Biochemical parameters were estimated in serum and pancreatic tissue samples. Histopathological studies and DNA fragmentation assay were carried out in isolated pancreatic tissue. The results of the study indicated that treatment of AESF and AEBF exhibited a significant dose dependent protective effect. Upon the treatment, anti-oxidant enzymes were significantly (*pless than 0.05) increased. Biochemical results were correlated with the histopathological findings. In addition, the DNA fragmentation assay showed an intact DNA in pancreatic cells of treated groups. In conclusion, berry fruit extracts exerted a potential protective effect against L-arginine induced damage in rat pancreas, at least in part, due to its antioxidant properties.

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 Naringenin Protects against Acute Pancreatitis in Two Experimental Models in Mice by NLRP3 and Nrf2/HO-1 Pathways

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Yong Li ◽  
Yiyuan Pan ◽  
Lin Gao ◽  
Jingzhu Zhang ◽  
Xiaochun Xie ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Interleukin 1 ◽  
Serum Levels ◽  
Pancreatic Tissue ◽  
Experimental Models ◽  
Receptor Protein ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Protective Effects ◽  
Mild Acute Pancreatitis

Background. Naringenin (Nar) is a type of flavonoid and has been shown to have anti-inflammatory and antioxidative properties. However, the effects of Nar on acute pancreatitis (AP) have not been well studied. In this study, we aimed to investigate the function of Nar in a mouse model of AP. Methods. Mild acute pancreatitis (MAP) was induced by caerulein (Cae), and severe acute pancreatitis (SAP) was induced by L-arginine in mice. Nar was administered intraperitoneally at doses of 25, 50, or 100 mg/kg following MAP induction and at a dose of 100 mg/kg following SAP induction. The serum levels of cytokines, lipase, and amylase were determined, and pancreatic and pulmonary tissues were harvested. Results. The serum levels of amylase, lipase, and cytokines were significantly decreased in both MAP and SAP models after Nar treatment. The malondialdehyde (MDA) levels of the pancreatic tissue was significantly reduced in both MAP and SAP after Nar treatment. In contrast, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total sulfhydryl (T-SH), and non-proteinsulthydryl (NP-SH) were markedly increased in both MAP and SAP after Nar treatment. The injury in pancreatic and pulmonary tissues was markedly improved as evidenced by the inhibited expression of myeloperoxidase, nod-like receptor protein 3, and interleukin 1 beta as well as the enhanced expression of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in pancreatic tissues. Conclusions. Nar exerted protective effects on Cae-induced MAP and L-arginine-induced SAP in mice, suggesting that Nar may be a potential therapeutic intervention for AP.

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 Tanshinone IIA Protects against Acute Pancreatitis in Mice by Inhibiting Oxidative Stress via the Nrf2/ROS Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Weiwei Chen ◽  
Chenchen Yuan ◽  
Yingying Lu ◽  
Qingtian Zhu ◽  
Xiaojie Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Mouse Models ◽  
Serum Amylase ◽  
Sodium Taurocholate ◽  
Pancreatic Tissue ◽  
Tanshinone Iia ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Nrf2 Knockout

Background. Danshen (Salvia miltiorrhiza Bunge) and its main active component Tanshinone IIA (TSA) are clinically used in China. However, the effects of TSA on acute pancreatitis (AP) and its potential mechanism have not been investigated. In this study, our objective was to investigate the protective effects of TSA against AP via three classic mouse models. Methods. Mouse models of AP were established by caerulein, sodium taurocholate, and L-arginine, separately. Pancreatic and pulmonary histopathological characteristics and serum amylase and lipase levels were evaluated, and changes in oxidative stress injury and the ultrastructure of acinar cells were observed. The reactive oxygen species (ROS) inhibitor N-Acetylcysteine (NAC) and nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice were applied to clarify the protective mechanism of the drug. Results. In the caerulein-induced AP model, TSA administration reduced serum amylase and lipase levels and ameliorated the histopathological manifestations of AP in pancreatic tissue. Additionally, TSA appreciably decreased ROS release, protected the structures of mitochondria and the endoplasmic reticulum, and increased the protein expression of Nrf2 and heme oxygenase 1 of pancreatic tissue. In addition, the protective effects of TSA against AP were counteracted by blocking the oxidative stress (NAC administration and Nrf2 knockout in mice). Furthermore, we found that TSA protects pancreatic tissue from damage and pancreatitis-associated lung injury in two additional mouse models induced by sodium taurocholate and by L-arginine. Conclusion. Our data confirmed the protective effects of TSA against AP in mice by inhibiting oxidative stress via the Nrf2/ROS pathway.

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