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

Pancreatology ◽  
2020 ◽  
Vol 20 ◽  
pp. S22-S23
Author(s):  
W. Chen ◽  
C. Yuan ◽  
Q. Zhu ◽  
J. Chen ◽  
D. Deng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Tanshinone Iia

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.

Stimulation of stellate cells by injured acinar cells: a model of acute pancreatitis induced by alcohol and fat (VLDL)

2009 ◽  
Vol 297 (6) ◽  
pp. G1163-G1171 ◽  
Author(s):  
Marco Siech ◽  
Zhengfei Zhou ◽  
Shaoxia Zhou ◽  
Bernd Bair ◽  
Andreas Alt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Acinar Cell ◽  
Cell Injury ◽  
Stellate Cell ◽  
Stellate Cells ◽  
Pancreatic Acinar Cell ◽  
Pancreatic Stellate Cells ◽  
Matrix Synthesis ◽  
Repair Mechanisms

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).

Role of Cytokines and Oxidative Stress in the Pathophysiology of Acute Pancreatitis: Therapeutical Implications

2002 ◽  
Vol 1 (4) ◽  
pp. 393-403 ◽  
Author(s):  
L.G. Gomez-Cambronero ◽  
L. Sabater ◽  
J. Pereda ◽  
N. Cassinello ◽  
B. Camps ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
And Oxidative Stress ◽  
Pathophysiology Of Acute Pancreatitis

Hypertriglyceridemia thalassemia syndrome

2018 ◽  
Vol 31 (7) ◽  
pp. 821-822
Author(s):  
Mili Jain ◽  
Wahid Ali ◽  
Brijendra Bahadur Singh ◽  
Nishant Verma ◽  
Ashutosh Kumar
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Nephrotic Syndrome ◽  
Early Recognition ◽  
Thalassemia Major ◽  
Rare Entity ◽  
Transfusion Therapy ◽  
Case Presentation ◽  
Coronary Diseases ◽  
Secondary Causes

Abstract Background Hypertriglyceridemia thalassemia syndrome is a rare entity with an unknown pathogenetic link. Case presentation We report a case of an 8-month-old female with thalassemia major and increased triglyceride (TG) levels. The clinical features were as in classical thalassemia except for a white discoloration of the plasma. After exclusion of familial triglyceridemia and secondary causes (hypothyroidism, nephrotic syndrome, drugs etc.), a diagnosis of hypertriglyceridemia thalassemia syndrome was made. Conclusions The high levels of TG in these patients are associated with oxidative stress and higher risk of acute pancreatitis and coronary diseases. An early recognition is thus essential. In our patient, the levels reduced after a transfusion therapy similar to previous reports.

scholarly journals High-Fat Diet Aggravates the Intestinal Barrier Injury via TLR4-RIP3 Pathway in a Rat Model of Severe Acute Pancreatitis

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Ying-ru Su ◽  
Yu-pu Hong ◽  
Fang-chao Mei ◽  
Chen-yang Wang ◽  
Man Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Inflammatory Response ◽  
Severe Acute Pancreatitis ◽  
High Fat Diet ◽  
Sodium Taurocholate ◽  
Intestinal Barrier ◽  
High Body Mass Index ◽  
High Fat ◽  
Junction Protein

Objective. For patients with severe acute pancreatitis (SAP), a high body mass index (BMI) increases the possibility of infection derived from the intestine. In this study, we evaluate whether TAK242 can alleviate severe acute pancreatitis-associated injury of intestinal barrier in high-fat diet-fed rats. Methods. A SAP model was established by retrograde injection of 5% sodium taurocholate into the biliary-pancreatic duct. Thirty Sprague-Dawley (SD) adult rats were randomly divided into five groups: standard rat chow (SRC) normal (SN), SRC SAP (SAP), high-fat diet normal (HN), HFD SAP (HSAP), and TLR4 inhibitor pretreatment HFD SAP (HAPT) groups. Intraperitoneal injection of 3 mg/kg TAK242 was administered 30 minutes before SAP model establishment in the HAPT group. Rats were sacrificed 12 hours after SAP modeling, followed by blood and pancreatic and distal ileum tissue collection for further analyses. Changes in the pathology responses of the rats in each group were assessed. Result. Analyses of serum amylase, lipase, cholesterol, triglyceride, IL-1β, IL-6, DAO, and serum endotoxin as well as tight junction protein expression including zonula occluden-1 and occludin indicated that high-fat diet aggravated SAP-induced intestinal barrier injury via increasing inflammatory response. In addition, the level of necroptosis was significantly higher in the SAP group compared with the SN group while the HSAP group exhibited more necroptosis compared with the SAP group, indicating the important role of necroptosis in pancreatitis-associated gut injury and illustrating that high-fat diet aggravated necroptosis of the ileum. Pretreatment with TLR4 inhibitor significantly alleviated inflammatory response and reduced necroptosis and level of oxidative stress while improving intestinal barrier function. Conclusion. High-fat diet aggravated SAP-induced intestinal barrier injury via inflammatory reactions, necroptosis, and oxidative stress. Inhibition of TLR4 by TAK242 reduced inflammation, alleviated necroptosis, and lowered the level of oxidative stress and then protected the intestinal barrier dysfunction from SAP in high-fat diet-fed rats.

Elucidating the role of oxidative stress in the therapeutic effect of rutin on experimental acute pancreatitis

2016 ◽  
Vol 50 (12) ◽  
pp. 1350-1360 ◽  
Author(s):  
Fabíula Francisca Abreu ◽  
Ana Carla Araújo Souza ◽  
Simone Aparecida Teixeira ◽  
Antônio Garcia Soares ◽  
Daiane Franco Teixeira ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Pancreatitis ◽  
Therapeutic Effect ◽  
Experimental Acute Pancreatitis
Sign in / Sign up

Export Citation Format

Share Document