The Combined Effects of Etanercept Plus Methylprednisolone on Pancreatic Oxidative Stress in Acute Pancreatitis Induced by Cerulein

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).

Download Full-text

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

Current Drug Targets - Inflammation & Allergy ◽

10.2174/1568010023344544 ◽

2002 ◽

Vol 1 (4) ◽

pp. 393-403 ◽

Cited By ~ 66

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

Download Full-text

Combined effects of repeated administration of Bretmont Wipeout (glyphosate) and Ultrazin (atrazine) on testosterone, oxidative stress and sperm quality of Wistar rats

Toxicology Mechanisms and Methods ◽

10.3109/15376516.2014.989349 ◽

2014 ◽

Vol 25 (1) ◽

pp. 70-80 ◽

Cited By ~ 35

Author(s):

Sunny O. Abarikwu ◽

Oghenetega F. Akiri ◽

Mojisola A. Durojaiye ◽

Alabi Adenike

Keyword(s):

Oxidative Stress ◽

Wistar Rats ◽

Sperm Quality ◽

Repeated Administration ◽

Combined Effects

Download Full-text

Hypertriglyceridemia thalassemia syndrome

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0171 ◽

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.

Download Full-text

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

Mediators of Inflammation ◽

10.1155/2019/2512687 ◽

2019 ◽

Vol 2019 ◽

pp. 1-13 ◽

Cited By ~ 2

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.

Download Full-text

Drivers of Oxidative Stress in Acute Pancreatitis

Journal of Parenteral and Enteral Nutrition ◽

10.1177/0148607111424410 ◽

2012 ◽

Vol 36 (1) ◽

pp. 24-35 ◽

Cited By ~ 13

Author(s):

Stephen A. McClave

Keyword(s):

Oxidative Stress ◽

Acute Pancreatitis

Download Full-text

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

Free Radical Research ◽

10.1080/10715762.2016.1247494 ◽

2016 ◽

Vol 50 (12) ◽

pp. 1350-1360 ◽

Cited By ~ 11

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

Download Full-text

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/7161592 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 26

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.

Download Full-text