Polyethylene Glycol 35 (PEG35) Protects against Inflammation in Experimental Acute Necrotizing Pancreatitis and Associated Lung Injury

Ferrero-Andrés, Ana; Panisello‐Roselló, Arnau; Serafín, Anna; Roselló‐Catafau, Joan; Folch-Puy, Emma

doi:10.3390/ijms21030917

Cited by 20 publications

(27 citation statements)

References 29 publications

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“…PEG35 administration is also protective against liver warm ischemia reperfusion injury [25]. This protection has been reviewed in other organs, such as pancreas in an inflammation model [26]. This protective effect was demonstrated in i.v.…”

Section: Preservation Solution Peg (Kb) Concentration (G/l)mentioning

confidence: 99%

“…This protective effect was demonstrated in i.v. PEG35 pre-treatment in rats [26]. Several studies reported the efficiency of PEGs in upregulating cell-survival pathways in different organs [27,28], resulting in the protection of the mitochondria, prevention of radical oxygen species (ROS) formation, cell swelling and oedema, and preservation of the cellular membrane, among others.…”

Section: Preservation Solution Peg (Kb) Concentration (G/l)mentioning

confidence: 99%

“…PEG35 is a suitable candidate to increase preservation quality of liver grafts subjected to any modality of dynamic preservation, such as HOPE or combined methodologies such as HOPE-COR-NMP, due to three main points: 1) PEGs are stable, nontoxic, non-immunogenic and water-soluble molecules, as recognized by FDA [ 11 ]; 2) PEG35 confers oncotic and cytoprotective properties to be used for liver transplantation as defined by ELTR [ 9 ]; and 3) PEG35 is protective against IRI in experimental hypothermic, normothermic and hyperthermic conditions [ 26 , 27 , 85 , 86 ].…”

Section: Hope-cor-nmp and Peg35mentioning

confidence: 99%

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Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Rosello

Silva

Castro

et al. 2020

IJMS

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Organ transplantation is a multifactorial process in which proper graft preservation is a mandatory step for the success of the transplantation. Hypothermic preservation of abdominal organs is mostly based on the use of several commercial solutions, including UW, Celsior, HTK and IGL-1. The presence of the oncotic agents HES (in UW) and PEG35 (in IGL-1) characterize both solution compositions, while HTK and Celsior do not contain any type of oncotic agent. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic and water-soluble polymers, which present a combination of properties of particular interest in the clinical context of ischemia-reperfusion injury (IRI): they limit edema and nitric oxide induction and modulate immunogenicity. Besides static cold storage (SCS), there are other strategies to preserve the organ, such as the use of machine perfusion (MP) in dynamic preservation strategies, which increase graft function and survival as compared to the conventional static hypothermic preservation. Here we report some considerations about using PEG35 as a component of perfusates for MP strategies (such as hypothermic oxygenated perfusion, HOPE) and its benefits for liver graft preservation. Improved liver preservation is closely related to mitochondria integrity, making this organelle a good target to increase graft viability, especially in marginal organs (e.g., steatotic livers). The final goal is to increase the pool of suitable organs, and thereby shorten patient waiting lists, a crucial problem in liver transplantation.

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Section: Preservation Solution Peg (Kb) Concentration (G/l)mentioning

confidence: 99%

Section: Preservation Solution Peg (Kb) Concentration (G/l)mentioning

confidence: 99%

Section: Hope-cor-nmp and Peg35mentioning

confidence: 99%

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Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Rosello

Silva

Castro

et al. 2020

IJMS

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“…Our group has recently demonstrated an anti-inflammatory role for PEG35 in an experimental model of severe necrotizing AP. In this sense, the therapeutic administration of PEG35 notably alleviated the severity of AP and protected against the associated lung inflammatory response[ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

Ferrero-Andrés¹,

Panisello‐Roselló²,

Roselló‐Catafau³

et al. 2020

WJG

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BACKGROUND Acute pancreatitis (AP) is a sudden inflammatory process of the pancreas that may also involve surrounding tissues and/or remote organs. Inflammation and parenchymal cell death are common pathological features of this condition and determinants of disease severity. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic water-soluble polymers widely used in biological, chemical, clinical and pharmaceutical settings. AIM To evaluate the protective effect of a 35-kDa molecular weight PEG (PEG35) on the pancreatic damage associated to cerulein-induced acute pancreatitis in vivo and in vitro . METHODS Wistar rats were assigned at random to a control group, a cerulein–induced AP group and a PEG35 treatment group. AP was induced by five hourly intraperitoneal injections of cerulein (50 μg/kg/bw), while the control animals received saline solution. PEG35 was administered intraperitoneally 10 minutes before each cerulein injection in a dose of 10 mg/kg. After AP induction, samples of pancreatic tissue and blood were collected for analysis. AR42J pancreatic acinar cells were treated with increasing concentrations of PEG35 prior to exposure with tumor necrosis factor α (TNFα), staurosporine or cerulein. The severity of AP was determined on the basis of plasma levels of lipase, lactate dehydrogenase activity, pancreatic edema and histological changes. To evaluate the extent of the inflammatory response, the gene expression of inflammation-associated markers was determined in the pancreas and in AR42J-treated cells. Inflammation-induced cell death was also measured in models of in vivo and in vitro pancreatic damage. RESULTS Administration of PEG35 significantly improved pancreatic damage through reduction on lipase levels and tissue edema in cerulein-induced AP rats. The increased associated inflammatory response caused by cerulein administration was attenuated by a decrease in the gene expression of inflammation-related cytokines and inducible nitric oxide synthase enzyme in the pancreas. In contrast, pancreatic tissue mRNA expression of interleukin 10 was markedly increased. PEG35 treatment also protected against inflammation-induced cell death by attenuating lactate dehydrogenase activity and modulating the pancreatic levels of apoptosis regulator protein BCL-2 in cerulein hyperstimulated rats. Furthermore, the activation of pro-inflammatory markers and inflammation-induced cell death in pancreatic acinar cells treated with TNFα, cerulein or staurosporine was significantly reduced by PEG35 treatment, in a dose-dependent manner. CONCLUSION PEG35 ameliorates pancreatic damage in cerulein-induced AP and AR42J-treated cells through the attenuation of the inflammatory response and associated cell death. PEG35 may be a valuable option in the management of AP.

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“…Interestingly, we have recently reported an anti-inflammatory role of 35-kDa molecular weight PEG (PEG35) in experimental AP and associated lung injury [ 15 ]. Intravenous administration of PEG35 was able to reduce the severity of the inflammatory damage and to improve outcomes when administered following the initiation of AP-associated systemic effects.…”

Section: Introductionmentioning

confidence: 99%

Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function

et al. 2020

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Polyethylene glycols (PEGs) are neutral polymers widely used in biomedical applications due to its hydrophilicity and biocompatibility. Exosomes are small vesicles secreted by nearly all cell types and play an important role in normal and pathological conditions. The purpose of this study was to evaluate the role of a 35-kDa molecular weight PEG (PEG35) on the modulation of exosome-mediated inflammation. Human macrophage-like cells THP-1, epithelial BICR-18, and CAPAN-2 cells were exposed to PEG35 prior to incubation with exosomes of different cellular origins. Exosome internalization was evaluated by confocal microscopy and flow cytometry. In another set of experiments, macrophages were treated with increasing concentrations of PEG35 prior to exposure with the appropriate stimuli: lipopolysaccharide, BICR-18-derived exosomes, or exosomes from acute pancreatitis-induced rats. Nuclear Factor Kappa B (NFκB) and Signal transducer and activator of transcription 3 (STAT3) activation and the expression levels of pro-inflammatory Interleukin 1β (IL1β) were determined. PEG35 administration significantly enhanced the internalization of exosomes in both macrophages and epithelial cells. Further, PEG35 ameliorated the inflammatory response induced by acute pancreatitis-derived exosomes by reducing the expression of IL1β and p65 nuclear translocation. Our results revealed that PEG35 promotes the cellular uptake of exosomes and modulates the pro-inflammatory effect of acute pancreatitis-derived vesicles through inhibition of NFκB, thus emphasizing the potential value of PEG35 as an anti-inflammatory agent for biomedical purposes.

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Polyethylene Glycol 35 (PEG35) Protects against Inflammation in Experimental Acute Necrotizing Pancreatitis and Associated Lung Injury

Cited by 20 publications

References 29 publications

Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Polyethylene glycol 35 ameliorates pancreatic inflammatory response in cerulein-induced acute pancreatitis in rats

Polyethylene Glycol 35 (PEG35) Modulates Exosomal Uptake and Function

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