Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis

Pérez, Salvador; Pereda, Javier; Sabater, Luís; Sastre, Juan

doi:10.1016/j.freeradbiomed.2014.08.008

Cited by 17 publications

(20 citation statements)

References 51 publications

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“…As is known, PAAF plays an important role during the progression of SAP. It contains a mass of toxic substances including tumor necrosis factor a, interleukin and endotoxin, which can induce pancreatic tissue necrosis and aggravate the inflammatory response [2][3][4][5]. Therefore, various treatment strategies that remove PAAF may be effective in treating SAP [25].…”

Section: Discussionmentioning

confidence: 99%

“…Pancreatic associated ascites fluid (PAAF) is known to play a critical role in the pathogenesis of SAP because it contains various Chen Luo and Qilin Huang have contributed equally to this study. toxic substances such as tumor necrosis factor, interleukin, endotoxin and so on [2][3][4][5]. Our previous clinical and experimental studies showed that abdominal paracentesis drainage (APD) attenuated the outcomes of SAP safely and effectively through removing PAAF [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

et al. 2020

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Our previous studies have shown that abdominal paracentesis drainage (APD) is a safe and effective strategy for patients with severe acute pancreatitis (SAP). However, the underlying mechanisms behind APD treatment remain poorly understood. Given that apoptosis is a critical pathological response of SAP, we here aim to investigate the effect of APD on cell apoptosis in pancreatic tissues during SAP and to explore its potential molecular mechanism. SAP was induced by 5% sodiumtaurocholate retrograde while APD group was inserted a drainage tube into the right lower abdomen of rats immediately after SAP induction. Histopathological staining, serum amylase, endotoxin and inflammatory mediators were measured. Cell apoptosis, apoptosis-related proteins and signaling pathway were also evaluated. Our results demonstrated that APD treatment significantly attenuated pancreatic damage and decreased the serum levels of amylase, endotoxin, TNF-α, IL-1 and IL-6 in rats with SAP. Notably, APD treatment enhanced cell apoptosis and reduced necrosis in pancreatic tissues, as evidenced by Tunnel staining, the increased pro-apoptosis proteins (Cleaved-caspase-3 and bax) and decreased anti-apoptosis protein (Bcl-2). Moreover, the effect of APD on cell apoptosis was further confirmed by the regulatory pathway of PI3K/AKT and NF-kB signaling pathway. These results suggest that APD attenuates the severity of SAP by enhancing cell apoptosis via suppressing PI3K/AKT signaling pathway. Our findings provide new insights for understanding the effectiveness of APD in patients with SAP. Keywords APD • Severe acute pancreatitis • Apoptosis • PI3K/AKT signaling pathway Abbreviations AKT(PKB) Protein kinase B ANOVA One-way analysis of variance APD Abdominal paracentesis drainage Bcl-2 B-cell lymphoma 2 Caspase3 Cysteine aspartic acid protease 3 ELISA Enzyme-linked immunosorbent assay IL Interleukin MAP Mild acute pancreatitis MODS Multiple organ dysfunction syndrome NF-kB Nuclear factor kappa-light-chain-enhancer of activated B cells PAAF Pancreatitis associated ascitic fluids PI3K Phosphatidylinositide 3-kinases SAP Severe acute pancreatitis SIRS Systemic inflammatory response syndrome TNF-α TNF-α

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

et al. 2020

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“…In conclusion, the current study [8] provides new information about the link between local pancreatic damage and the subsequent systemic inflammatory response, providing direct evidence on the role of free Hb in the pathogenesis of acute pancreatitis.…”

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confidence: 69%

“…Since then, xanthine oxidase [16], circulating neutrophils [17], nitric oxide synthase [18], and depletion of superoxide dismutase [19] and glutathione [20] have been suggested as potential triggers of oxidative stress, but the final source remains unclear. Although the study by Pérez et al [8] does not address this question directly, its findings strongly suggest a pivotal role as a source of oxidant stress for free Hb.…”

mentioning

confidence: 93%

“…The paper in this issue of Free Radical Biology & Medicine entitled "Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis," by Pérez and colleagues [8], provides evidence that free Hb also is involved in the pathogenesis of severe acute pancreatitis. Using an experimental model of bile salt-induced pancreatitis in rats, the authors demonstrate the hemolytic capacity of the ascitic fluid generated in the early stages of the disease.…”

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confidence: 99%

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Commentary on “Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis”

Closa

2015

Free Radical Biology and Medicine

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Obesity causes PGC‐1α deficiency in the pancreas leading to marked IL‐6 upregulation via NF‐κB in acute pancreatitis

Pérez

Rius‐Pérez

Finamor

et al. 2018

The Journal of Pathology

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Obesity is associated with local and systemic complications in acute pancreatitis. PPARγ co-activator 1α (PGC-1α) is a transcriptional co-activator and master regulator of mitochondrial biogenesis that exhibits dysregulation in obese subjects. Our aims were 1) to study PGC-1α levels in pancreas from lean or obese rats and mice with acute pancreatitis; and 2) to determine the role of PGC-1α in the inflammatory response during acute pancreatitis elucidating the signaling pathways regulated by PGC-1α. Lean and obese Zucker rats and lean and obese C57BL6 mice were used first, and subsequently wild-type and PGC-1α knock-out (KO) mice with cerulein-induced pancreatitis were used to assess the inflammatory response and expression of target genes. Ppargc1a mRNA and protein levels were markedly down-regulated in pancreas of obese mice versus lean mice. PGC-1α protein levels increased in pancreas of lean mice with acute pancreatitis, but not in obese mice with pancreatitis. Il6 mRNA levels were dramatically up-regulated in pancreas of PGC-1α KO mice after cerulein-induced pancreatitis in comparison with wild type mice with pancreatitis. Edema and the inflammatory infiltrate were more intense in pancreas from PGC-1α KO mice than in wild type mice. The lack of PGC-1α markedly enhanced nuclear translocation of phospho-p65 and recruitment of p65 to Il6 promoter. PGC-1α bound phospho-p65 in pancreas during pancreatitis in wild type mice. Glutathione depletion in cerulein-induced pancreatitis was more severe in KO mice than in wild type mice. PGC-1α KO mice with pancreatitis, but not wild type mice, exhibited increased MPO activity in the lungs together with alveolar wall thickening and collapse, which were abrogated by blockade of the IL-6 receptor gp130 with LMT-28. In conclusion, obese rodents exhibit PGC-1α deficiency in the pancreas. PGC-1α acts as selective repressor of NF-κB towards IL-6 in pancreas. PGC-1α deficiency markedly enhanced NF-κB-mediated up-regulation of Il6 in pancreas in pancreatitis, leading to severe inflammatory response.

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Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis

Cited by 17 publications

References 51 publications

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Abdominal paracentesis drainage attenuates severe acute pancreatitis by enhancing cell apoptosis via PI3K/AKT signaling pathway

Commentary on “Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis”

Obesity causes PGC‐1α deficiency in the pancreas leading to marked IL‐6 upregulation via NF‐κB in acute pancreatitis

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