Oxidative stress in acute pancreatitis: lost in translation?

Armstrong, J. A.; Cash, Nicole; Soares, Pedro Marcos Gomes; Souza, Michael; Sutton, Robert; Criddle, David N.

doi:10.3109/10715762.2013.835046

Cited by 54 publications

(42 citation statements)

References 160 publications

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“…It has been suggested that excessive amount of ROS could evolve towards an oxidative stress condition, and would damage macromolecules like proteins, DNA and lipids, finally leading to cell damage [1,2,3,4]. Therefore, oxidative stress containment is paramount to protect cell physiology.…”

Section: Introductionmentioning

confidence: 99%

Melatonin induces the expression of Nrf2-regulated antioxidant enzymes via PKC and Ca2+ influx activation in mouse pancreatic acinar cells

Santofimia‐Castaño

Ruy

Garcia-Sanchez

et al. 2015

Free Radical Biology and Medicine

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The goal of this study was to evaluate the potential activation of the nuclear factor erythroid 2-related factor and the antioxidant-responsive element (Nrf2-ARE) signaling pathway in response to melatonin in isolated mouse pancreatic acinar cells. Changes in intracellular free Ca(2+) concentration were followed by fluorimetric analysis of fura-2-loaded cells. The activations of PKC and JNK were measured by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was employed to detect the expression of Nrf2-regulated antioxidant enzymes. Immunocytochemistry was employed to determine nuclear location of phosphorylated Nrf2, and the cellular redox state was monitored following MitoSOX Red-derived fluorescence. Our results show that stimulation of fura-2-loaded cells with melatonin (1 µM to 1 mM), in the presence of Ca(2+) in the extracellular medium, induced a slow and progressive increase of [Ca(2+)](c) toward a stable level. Melatonin did not inhibit the typical Ca(2+) response induced by CCK-8 (1 nM). When the cells were challenged with indoleamine in the absence of Ca(2+) in the extracellular solution (medium containing 0.5 mM EGTA) or in the presence of 1 mM LaCl(3), to inhibit Ca(2+) entry, we could not detect any change in [Ca(2+)](c). Nevertheless, CCK-8 (1 nM) was able to induce the typical mobilization of Ca(2+). When the cells were incubated with the PKC activator PMA (1 µM) in the presence of Ca(2+) in the extracellular medium, we observed a response similar to that noted when the cells were challenged with melatonin 100 µM. However, in the presence of Ro31-8220 (3 µM), a PKC inhibitor, stimulation of cells with melatonin failed to evoke changes in [Ca(2+)]c. Immunoblots, using an antibody specific for phospho-PKC, revealed that melatonin induces PKCα activation, either in the presence or in the absence of external Ca(2+). Melatonin induced the phosphorylation and nuclear translocation of the transcription factor Nrf2, and evoked a concentration-dependent increase in the expression of the antioxidant enzymes NAD(P)H-quinone oxidoreductase 1, catalytic subunit of glutamate-cysteine ligase, and heme oxygenase-1. Incubation of MitoSOX Red-loaded pancreatic acinar cells in the presence of 1 nM CCK-8 induced a statistically significant increase in dye-derived fluorescence, reflecting an increase in oxidation, that was abolished by pretreatment of cells with melatonin (100 µM) or PMA (1 µM). On the contrary, pretreatment with Ro31-8220 (3 µM) blocked the effect of melatonin on CCK-8-induced increase in oxidation. Finally, phosphorylation of JNK in the presence of CCK-8 or melatonin was also observed. We conclude that melatonin, via modulation of PKC and Ca(2+) signaling, could potentially stimulate the Nrf2-mediated antioxidant response in mouse pancreatic acinar cells.

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Section: Introductionmentioning

confidence: 99%

Melatonin induces the expression of Nrf2-regulated antioxidant enzymes via PKC and Ca2+ influx activation in mouse pancreatic acinar cells

Santofimia‐Castaño

Ruy

Garcia-Sanchez

et al. 2015

Free Radical Biology and Medicine

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“…Oxidative stress is involved in the pathogenesis of AP [19]. Previous studies have shown that oxygen free radicals (OFR)-induced lipid peroxidation and changes in GSH metabolism occur at an early stage in the course of AP [20, 21].…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects of Shen-Fu Injection on Experimental Acute Pancreatitis in a Rat Model

Huang

Cao

2014

Oxidative Medicine and Cellular Longevity

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Objectives. In the present study, we investigated the protective effects of Shen-Fu injection (SFI) on a caerulein-induced rat pancreatitis (AP) model. Methods. SFI was given to rats in the SFI treated group through intraperitoneal injection. Blood and pancreas samples were collected for serological and histopathological studies. Results. Our results showed that AP caused significant decrease in tissue glutathione (GSH) and serum IL-4 and IL-10, while pancreatic malondialdehyde (MDA) and myeloperoxidase (MPO) were increased. Furthermore, TNF-α, IL-1β, amylase, and lipase levels were also significantly increased. On the other hand, SFI treatment reserved all these biochemical indices as well as histopathologic alterations that were induced by caerulein. Conclusion. Our findings suggest that the SFI protects against caerulein-induced AP in rats via modulation of cytokines, oxidative stress, and Nuclear Factor-kappa B (NF-κB) activity.

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“…Recent reports have highlighted the role of activation of inflammatory cytokines and signal pathways in pancreatic tissues during the process of SAP[4,5]. Activation of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and infiltration of inflammatory cells in early SAP can lead to pathological injury not only in pancreatic tissue but also in extra-pancreatic organs, through activation of downstream inflammatory mediators by the amplification of a series of cascade reactions[6].…”

Section: Introductionmentioning

confidence: 99%

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

Wang

Guo

et al. 2016

WJG

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AIMTo determine the effects of ω-3 fatty acids (ω-3FA) on the toll-like receptor 4 (TLR4)/nuclear factor κB p56 (NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis (SAP).METHODSA total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay.RESULTSThe expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group (P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h (P < 0.05).CONCLUSIONDuring the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

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Oxidative stress in acute pancreatitis: lost in translation?

Cited by 54 publications

References 160 publications

Melatonin induces the expression of Nrf2-regulated antioxidant enzymes via PKC and Ca2+ influx activation in mouse pancreatic acinar cells

Melatonin induces the expression of Nrf2-regulated antioxidant enzymes via PKC and Ca2+ influx activation in mouse pancreatic acinar cells

The Protective Effects of Shen-Fu Injection on Experimental Acute Pancreatitis in a Rat Model

Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

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