Lipid Peroxidation Inhibition Reduces NF-κB Activation and Attenuates Cerulein-induced Pancreatitis

Altavilla, Domenica; Famulari, Ciro; Passaniti, Maria; Campo, Giuseppe M.; Macrì, Antonio; Seminara, Paolo; Marini, Herbert; Calò, Margherita; Santamaria, L. B.; Bono, Daniela; Venuti, Francesco S.; Mioni, Chiara; Leone, Sheila; Guarini, Salvatore; Squadrito, Francesco

doi:10.1080/1071576031000070093

Cited by 34 publications

(26 citation statements)

References 29 publications

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“…Among these, ROS, which can function as second messengers, were closely associated with NF-B-mediated inflammation during AP pathogenesis. Oxidative stress-induced NF-B activation has been demonstrated in a number of animal models of AP, including caerulein-induced AP (Gukovsky et al, 1998;Altavilla et al, 2003), taurochoate-induced AP (Vaquero et al, 2001), and obstruction-induced AP (Ramudo et al, 2005). In the present study, it was clear by the reduced levels of GSH and nitrotyrosine that the pancreatic tissues afflicted with AP were under oxidative stress; these changes could be reversed by losartan treatment.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Chan¹,

Leung²

2007

J Pharmacol Exp Ther

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Angiotensin II is a key mediator of inflammation, and nuclear factor-B (NF-B) plays a critical role in various inflammatory diseases, including acute pancreatitis (AP). This study sought to elucidate the mechanism mediating angiotensin II involvement in angiotensin II type 1 (AT 1 ) receptor-mediated NF-B activation, and ultimately in proinflammatory actions of AP pathogenesis. A rat model of obstructive pancreatitis was induced by ligation of the common biliopancreatic duct. Pancreatic injury was determined by assessing pancreatic histology, myeloperoxidase activity, and serum interleukin-6. Protein levels of pancreatic angiotensinogen and AT 1 receptor as well as NF-B inhibitory subunits (IB␣ and IB␤) and phospho-NF-B p65, B-related proteins (intercellular adhesion molecule-1, cyclooxygenas-2, and interleukin-1), and NADPH oxidase isoforms p67 and p22 were examined by Western blot. Nuclear B binding activity and degree of oxidative stress were determined by electrophoretic mobility shift assay and glutathione/nitrotyrosine examination, respectively. The effects of losartan, an AT 1 receptor antagonist, on NF-B-mediated proinflammatory actions were also assessed. Induction of AP was associated with a time-dependent increase in pancreatic angiotensinogen levels. AT 1 receptor blockade with losartan improved the pancreatic histological damage, myeloperoxidase activity, and serum interleukin-6. Losartan treatment also reduced AP-associated depletion of IB␤ and elevation of phospho-NF-B p65 protein expression as well as the enhanced nuclear B binding activity and elevated levels of B-related proteins. In addition, losartan treatment suppressed pancreatic glutathione and nitrotyrosine levels, which were consistent with decreased NADPH oxidase expression. These data provide substantial evidence that angiotensin II is involved in AT 1 receptor-mediated NADPH oxidase-dependent NF-B activation; thus, it might ultimately promote proinflammatory actions during AP pathogenesis.Acute pancreatitis (AP) is a pathological state with various degrees of severity, ranging from edematous AP to hemorrhagic necrotic AP. The mortality rate, which approaches 20%, is closely associated with systemic complications, manifesting as acute respiratory distress syndrome and multiple organ dysfunction syndromes. An approximate 80% of cases can be etiologically determined, whereas 20% are considered idiopathic (UK Working Party on Acute Pancreatitis, 2005). Accumulating data suggest that the renin-angiotensin system (RAS) plays an important role in AP pathogenesis. During caerulein-induced pancreatitis, major components of a local pancreatic RAS were markedly up-regulated (Tsang et al., 2004a). Treatment with RAS blockers could ameliorate pancreatic oxidative stress and histological deterioration observed in experimental AP Tsang et al., 2003). A specific antagonist for the AT 1 receptor, 2-butyl-4-chloro-1-[p-(o-1H-tetrazol-5-ylphenyl) benzyl] imidazole-5-methanol monopotassium salt (C 22 H 23 ClN 6 O) (losartan), has been shown to pr...

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Section: Discussionmentioning

confidence: 99%

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Chan¹,

Leung²

2007

J Pharmacol Exp Ther

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“…NFκb with subsequent up-regulation of the expression of genes coding for a variety inflammatory factors including cytokines and chemokines such as TNF-α, IL-1, IL-6, IL-8. In acute pancreatitis [25] , NF-κb activation can be inhibited by blocking the degradation of Iκb, which has been shown to ameliorate the severity of pancreatitis [26] . During acute pancreatitis, lung injury is associated with the accumulation of neutrophils within the interstitial and alveolar spaces.…”

Section: Discussionmentioning

confidence: 99%

Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats

Chen¹,

Li²,

Wu³

et al. 2008

WJG

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AIM:To observe the effect of proteasome inhibitor MG-132 on severe acute pancreatitis (SAP) and associated lung injury of rats. METHODS: Male adult SD rats were randomly divided into SAP group, sham-operation group, and MG-132 treatment group. A model of SAP was established by injection of 5% sodium taurocholate into the biliarypancreatic duct of rats. The MG-132 group was pretreated with 10 mg/kg MG-132 intraperitoneally (ip) 30 min before the induction of pancreatitis. The changes in serum amylase, myeloperoxidase (MPO) activity of pancreatic and pulmonary tissue were measured. The TNF-α level in pancreatic cytosolic f ra c t i o n s wa s a s s aye d w i t h a n e n z y m e -l i n ke d immunosorbent assay (ELISA) kit. Meanwhile, the pathological changes in both pancreatic and pulmonary tissues were also observed. RESULTS: MG-132 significantly decreased serum amylase, pancreatic weight/body ratio, pancreatic TNF-α level, pancreatic and pulmonary MPO activity (P < 0.05). Histopathological examinations revealed that pancreatic and pulmonary samples from rats pretreated with MG-132 demonstrated milder edema, cellular damage, and inflammatory activity (P < 0.05). CONCLUSION:The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.© 2008 The WJG Press. All rights reserved. Chen X, Li SL, Wu T, Liu JD. Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats.

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“…For example, there is evidence that NF-κB plays a crucial role in the initiation of AP, not only in pancreatic acinar cells and monocytes/ macrophages but also in specific distant organs, such as the lung. NF-κB is able to mediate a variety of inflammatory mediators involved in AP, including cytokines and adhesion molecules [11][12][13] . In addition, intercellular adhesion molecule-1 (ICAM-1) has been reported to be up-regulated and involved in the evolution of acute pancreatitis by recruiting leukocytes into the area of inflammation [14,15] .…”

Section: Introductionmentioning

confidence: 99%

Pioglitazone attenuates the severity of sodium taurocholate-induced severe acute pancreatitis

Xu¹

2007

WJG

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AIM:To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ) ligand, on development of severe acute pancreatitis (SAP) and expression of nuclear factor-kappa B (NF-κB) and intercellular adhesion molecule-1 (ICAM-1) in the pancreas. METHODS:Male Sprague-Dawley (SD) rats (160-200 g) were randomly allocated into three groups (n = 18 in each group): severe acute pancreatitis group, pioglitazone group, sham group. SAP was induced by retrograde infusion of 1 mL/kg body weight 5% sodium taurocholate (STC) into the biliopancreatic duct of male SD rats. Pioglitazone was injected intraperitoneally two hours piror to STC infusion. Blood and ascites were obtained for detecting amylase and ascitic capacity. Pancreatic wet/dry weight ratio, expression of NF-κB and ICAM-1 in pancreatic tissues were detected by immunohistochemical staining. Pancreatic tissue samples were stained with hematoxylin and eosin (HE) for routine optic microscopy. RESULTS:Sham group displayed normal pancreatic structure. SAP group showed diffuse hemorrhage, necrosis and severe edema in focal areas of pancreas. There was obvious adipo-saponification in abdominal cavity. Characteristics such as pancreatic hemorrhage, necrosis, severe edema and adipo-saponification were found in pioglitazone group, but the levels of those injuries were lower in pioglitazone group than those in SAP group. The wet/dry pancreatic weight ratio, ascetic capacity, serum and ascitic activities of anylase in the SAP group were significantly higher than those in the sham group and pioglitazone group respectively (6969.50 ± 1368.99 vs 2104.67 ± 377.16, 3.99 ± 1.22 vs 2.48 ± 0.74, P < 0.01 or P < 0.05). According to Kusske criteria, the pancreatic histologic score showed that interstitial edema, inflammatory infiltration, parenchyma necrosis and parenchyma hommorrhage in SAP group significantly differed from those in the sham group and pioglitazone group (7.17 ± 1.83 vs 0.50 ± 0.55, 7.67 ± 0.82 vs 6.83 ± 0.75, P < 0.01, P < 0.05.The expression of NF-κB and ICAM-1 in sham group was lower than that in SAP group and pioglitazone group (0.50 ± 0.55 vs 33 ± 1.21, P < 0.01). There was a significant difference in the expression of NF-κB and ICAM-1 between SAP group and pioglitazone group (7.50 ± 1.05 vs 11.33 ± 1.75, 0.80 ± 0.53 vs 1.36 ± 0.54, P < 0.01 or P < 0.05) at 12 h after the induction of pancreatitis. CONCLUSION:

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Lipid Peroxidation Inhibition Reduces NF-κB Activation and Attenuates Cerulein-induced Pancreatitis

Cited by 34 publications

References 29 publications

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Angiotensin II Type 1 Receptor-Dependent Nuclear Factor-κB Activation-Mediated Proinflammatory Actions in a Rat Model of Obstructive Acute Pancreatitis

Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats

Pioglitazone attenuates the severity of sodium taurocholate-induced severe acute pancreatitis

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