Potential role of reactive oxygen species in pancreatitis-associated multiple organ dysfunction

Shi, Changbin; Andersson, Roland; Zhao, Xia; Wang, Xiangdong

doi:10.1159/000087063

Cited by 56 publications

(34 citation statements)

References 71 publications

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“…Genetic or pharmacologic blockade of PARP inhibits necrosis and demonstrates a reduced pancreatitis response (43). In addition to the passive ATP depletion-mediated mechanisms, several active mechanisms (for example, oxidative stress, calcium overload, mitochondrial permeability transition pore opening and cathepsin release) also participate in the regulation of the necrotic process in AP (34,44,45). The actual mechanisms of necrosis involved in the development of sequential cellular and organ response in AP need further investigation.…”

Section: Necrosismentioning

confidence: 99%

Cell Death and DAMPs in Acute Pancreatitis

Kang

Lotze

Zeh

et al. 2014

Mol Med

125

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The pancreas is a dual-purpose gland with exocrine and endocrine functions. The exocrine pancreas produces digestive proteases in inactive proenzyme form, namely zymogens. The pancreas is normally able to protect itself from zymogen activation by synthesis of protease inhibitors such as pancreatic secretory trypsin inhibitor and serine protease inhibitor (for example, SPINK1/Spink3). By contrast, pancreatic autodigestion and subsequent AP is initiated once these defenses are impaired. In studies of rodent models (for example, repetitive cerulein or L-arginine injections, choline-deficient ethionine supplementation [CDE] diet, perfusion of taurocholate into the biliary or pancreatic duct and surgical ligation or infusion of pancreatic duct models), some essential pathogenic AP events have been identified (see Figure 1) (15,16).The development of AP involves a complex cascade of events (17), which start with injury or disruption of the pan- Cell Death and DAMPs in Acute PancreatitisRui Kang, Michael T Lotze, Herbert J Zeh, Timothy R Billiar, and Daolin Tang Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America Cell death and inflammation are key pathologic responses of acute pancreatitis (AP), the leading cause of hospital admissions for gastrointestinal disorders. It is becoming increasingly clear that damage-associated molecular pattern molecules (DAMPs) play an important role in the pathogenesis of AP by linking local tissue damage to systemic inflammation syndrome. Endogenous DAMPs released from dead, dying or injured cells initiate and extend sterile inflammation via specific pattern recognition receptors. Inhibition of the release and activity of DAMPs (for example, high mobility group box 1, DNA, histones and adenosine triphosphate) provides significant protection against experimental AP . Moreover, increased serum levels of DAMPs in patients with AP correlate with disease severity. These findings provide novel insight into the mechanism, diagnosis and management of AP . DAMPs might be an attractive therapeutic target in AP.

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Section: Necrosismentioning

confidence: 99%

Cell Death and DAMPs in Acute Pancreatitis

Kang

Lotze

Zeh

et al. 2014

Mol Med

125

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“…Acute pancreatitis is an inflammatory process in the pancreas, and oxygen free radicals have been implicated as an important factor in the associated tissue destruction in both the initiation and progression of AP (Telek et al, 1999;Kyu et al, 2003;Shi et al, 2005;Genovese et al, 2006). In addition, oxidative stress was documented in pancreatic tissue by means of methods showing accumulation of products of lipid peroxidation and occurrence of oxidatively modified proteins, with concomitant depletion of enzymatic and low molecular weigh antioxidants (Reinheckel et al, 1998;Dabrowski et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, pro-inflammatory cytokines and oxidative stress trigger common signal transduction pathways that lead to amplification of the inflammatory cascade (Shi et al, 2005;Pereda et al, 2006). Furthermore, pro-inflammatory cytokines, in particularly TNF-α, and oxidative stress promote each other generating a vicious circle in AP.…”

Section: Discussionmentioning

confidence: 99%

“…Actived macrophages release pro-inflammatory cytokines in response to the local damage of the pancreas. Moreover, increased oxidative stress appeared during pancreatitis in the course of AP (Dabrowski et al, 1999;Telek et al, 1999;Abu-Zidan et al, 2000;Shi et al, 2005). At present there are evidences of a synergy or the relationship between oxidative stress and pro-inflammatory cytokines in development of the inflammatory response in AP Pereda et al, 2006).…”

Section: Introductionmentioning

confidence: 95%

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

Günay¹,

Kılıç²,

AMANVERMEZ³

2011

jecm

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KeywordsEtanercept Methylprednisolone Acute pancreatitis Oxidative stress Malondialdehyde Protein carbonyls ARTICLE INFO ABSTRACTWhether etanercept plus metylprednisolone reduce pancreatic oxidative stress and injury during pancreatitis is unknown well. The aim of this study was to examine the therapeutic effects of etanercept and methylprednisolone (MP) on acute pancreatitis and oxidative stress in acute pancreatitis (AP) induced by cerulein in a rat model. The study was performed with 48 rats divided into 6 groups (n = 8/group): 1-sham, 2-cerulein-induced pancreatitis (over 10 hours), 3-cerulein-pancreatitis (over 20 hours), 4-etanercept (5 mg/ kg, i.p.), 5-methylprednisolone (10 mg/kg, i.m.), 6-etanercept plus methylprednisolone. Also, the rats in groups 4, 5, and 6 were cerulein-induced pancreatitis at 20 hours. After the treatment, the pancreas and blood were taken for histopathological and biochemical analysis. All cerulein-treated rats developed biochemical and pathological acute pancreatitis after 10-20 hours. The markers of oxidative stress such as protein carbonyls, lipid peroxidation, and myeloperoxidase (mpo) in the pancreas tissues were increased in the group 2 and 3, but these were lower in etanercept and MP-treated rats compared to groups 3. Pancreatic mpo activity was considerably reduced in pancreas tissues at 20 h after the administration of etanercept plus metylprednisolone in the group 6 compared to group 3. In AP induced by cerulein, the treatment of etanercept plus methylprednisolone may ameliorate pancreatic oxidative stress in rats.

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“…Effected by increased phospholipase during acute pancreatitis condition, the cell membrane phospholipids decompose arachidonic acid, evoke TXA2 increase, lead to platelet aggregation, thrombosis, induce platelet deformation, adhesion, result in coagulation dysfunction, precipitate pancreatic ischemia and microcirculation, and increase pancreatic pathology injury [132]. In addition, it can promote neutrophil cell activation, release ROS, injure capillary endothelial cells, result in increased capillary permeability, and plasma extravasation [133].…”

Section: Thromboxane A2 (Txa2)mentioning

confidence: 99%

Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis

Uhlmann¹

2012

Acute Pancreatitis

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Potential role of reactive oxygen species in pancreatitis-associated multiple organ dysfunction

Cited by 56 publications

References 71 publications

Cell Death and DAMPs in Acute Pancreatitis

Cell Death and DAMPs in Acute Pancreatitis

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

Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis

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