scholarly journals Protective Effect of Intravenous High Molecular Weight Polyethylene Glycol on Fatty Liver Preservation

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Mohamed Bejaoui ◽  
Eirini Pantazi ◽  
Emma Folch-Puy ◽  
Arnau Panisello ◽  
María Calvo ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Liver Injury ◽  
High Molecular Weight ◽  
Intravenous Administration ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Water Soluble ◽  
Isolated Perfused Rat Liver ◽  
Cold Ischemia ◽  
Liver Preservation

Ischemia reperfusion injury (IRI) leads to significant tissue damage in liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proved their effectiveness against IRI. The objective of our study was to investigate the potential protective effects of intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) in steatotic livers subjected to cold ischemia reperfusion. In this study, we used isolated perfused rat liver model to assess the effects of PEG 35 intravenous administration after prolonged cold ischemia (24 h, 4°C) and after reperfusion (2 h, 37°C). Liver injury was measured by transaminases levels and mitochondrial damage was determined by confocal microscopy assessing mitochondrial polarization (after cold storage) and by measuring glutamate dehydrogenase activity (after reperfusion). Also, cell signaling pathways involved in the physiopathology of IRI were assessed by western blot technique. Our results show that intravenous administration of PEG 35 at 10 mg/kg ameliorated liver injury and protected the mitochondria. Moreover, PEG 35 administration induced a significant phosphorylation of prosurvival protein kinase B (Akt) and activation of cytoprotective factors e-NOS and AMPK. In conclusion, intravenous PEG 35 efficiently protects steatotic livers exposed to cold IRI.

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

2020 ◽  
Vol 21 (16) ◽  
pp. 5703 ◽  
Author(s):  
Arnau Panisello Rosello ◽  
Rui Teixeira da Silva ◽  
Carlos Castro ◽  
Raquel G. Bardallo ◽  
Maria Calvo ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Water Soluble ◽  
Liver Graft ◽  
Liver Preservation ◽  
Hypothermic Preservation ◽  
Graft Preservation ◽  
Abdominal Organs ◽  
Good Target

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.

scholarly journals Aldehyde Dehydrogenase 2 (ALDH2) in Rat Fatty Liver Cold Ischemia Injury

2018 ◽  
Vol 19 (9) ◽  
pp. 2479 ◽  
Author(s):  
Arnau Panisello-Roselló ◽  
Norma Alva ◽  
Marta Flores ◽  
Alexandre Lopez ◽  
Carlos Castro Benítez ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Reperfusion Injury ◽  
Aldehyde Dehydrogenase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Related Factor ◽  
Aldehyde Dehydrogenase 2 ◽  
Cold Ischemia ◽  
Liver Preservation

Institut George Lopez-1 (IGL-1) and Histidine-tryptophan-ketoglutarate (HTK) solutions are proposed as alternatives to UW (gold standard) in liver preservation. Their composition differs in terms of the presence/absence of oncotic agents such as HES or PEG, and is decisive for graft conservation before transplantation. This is especially so when fatty (steatotic) livers are used since these grafts are more vulnerable to ischemia insult during conservation. Their composition determines the extent of the subsequent reperfusion injury after transplantation. Aldehyde dehydrogenase-2 (ALDH2), a mitochondrial enzyme, has been reported to play a protective role in warm ischemia-reperfusion injury (IRI), but its potential in fatty liver cold ischemic injury has not yet been investigated. We evaluated the relevance of ALDH2 activity in cold ischemia injury when fatty liver grafts from Zucker Obese rats were preserved in UW, HTK, and IGL-1 solutions, in order to study the mechanisms involved. ALDH2 upregulation was highest in livers preserved in IGL-1. It was accompanied by a decrease in transaminases, apoptosis (Caspase 3 and TUNEL assay), and lipoperoxidation, which was concomitant with the effective clearance of toxic aldehydes such as 4-hydroxy-nonenal. Variations in ATP levels were also determined. The results were consistent with levels of NF-E2 p45-related factor 2 (Nrf2), an antioxidant factor. Here we report for the first time the relevance of mitochondrial ALDH2 in fatty liver cold preservation and suggest that ALDH2 could be considered a potential therapeutic target or regulator in clinical transplantation.

Natural resistance to liver cold ischemia-reperfusion injury associated with the hibernation phenotype

2005 ◽  
Vol 288 (3) ◽  
pp. G473-G480 ◽  
Author(s):  
Susanne L. Lindell ◽  
Shawna L. Klahn ◽  
Timothy M. Piazza ◽  
Martin J. Mangino ◽  
Jose R. Torrealba ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ground Squirrels ◽  
Natural Resistance ◽  
Cold Ischemia ◽  
Liver Preservation ◽  
University Of Wisconsin ◽  
Ldh Release ◽  
Rat Livers

The success of liver grafts is currently limited by the length of time organs are cold preserved before transplant. Novel insights to improve viability of cold-stored organs may emerge from studies with animals that naturally experience low body temperatures (Tb) for extended periods. In this study, we tested whether livers from hibernating ground squirrels tolerate cold ischemia-warm reperfusion (cold I/R) for longer times and with better quality than livers from rats or summer squirrels. Hibernators were used when torpid (Tb < 10°C) or aroused (Tb = 37°C). Livers were stored at 4°C in University of Wisconsin solution for 0–72 h and then reperfused with 37°C buffer in vitro. Lactate dehydrogenase (LDH) release after 60 min was increased 37-fold in rat livers after 72 h cold I/R but only 10-fold in summer livers and approximately three- to sixfold in torpid and aroused hibernator livers, despite twofold higher total LDH content in livers from hibernators compared with rats or summer squirrels. Reperfusion for up to 240 min had the least effect on LDH release in livers from hibernators and the greatest effect in rats. Compared with rats or summer squirrels, livers from hibernators after 72 h cold I/R showed better maintenance of mitochondrial respiration, bile production, and sinusoidal lining cell viability, as well as lower vascular resistance and Kupffer cell phagocytosis. These results demonstrate that the hibernation phenotype in ground squirrels confers superior resistance to liver cold I/R injury compared with rats and summer squirrels. Because hibernation-induced protection is not dependent on animals being in the torpid state, the mechanisms responsible for this effect may provide new strategies for liver preservation in humans.

scholarly journals The influence of FGF2 high molecular weight (HMW) isoforms in the development of cardiac ischemia–reperfusion injury

2010 ◽  
Vol 48 (6) ◽  
pp. 1245-1254 ◽  
Author(s):  
Siyun Liao ◽  
Janet R. Bodmer ◽  
Mohamad Azhar ◽  
Gilbert Newman ◽  
J. Douglas Coffin ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Reperfusion Injury ◽  
High Molecular Weight ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cardiac Ischemia

Effect of High Molecular Weight Water-Soluble Chitosan on the Trabecular Bone and Thickness in Ovariectomized Rats

2007 ◽  
Vol 29 (3-4) ◽  
pp. 439-449 ◽  
Author(s):  
Han-Jung Chae ◽  
Geun-Youn Lee ◽  
Sun-Kyung Yang ◽  
Do-Sung Kim ◽  
Ki-Jung Yun ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Trabecular Bone ◽  
High Molecular Weight ◽  
Water Soluble ◽  
Ovariectomized Rats

Interaction of Streptococcus mutans Glucosyltransferases with Teichoic Acids

1980 ◽  
Vol 29 (2) ◽  
pp. 376-382
Author(s):  
H. K. Kuramitsu ◽  
L. Wondrack ◽  
M. McGuinness
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Streptococcus Mutans ◽  
Teichoic Acid ◽  
Lipoteichoic Acid ◽  
Water Soluble ◽  
Heat Inactivation ◽  
Teichoic Acids ◽  
Insoluble Glucan

The Streptococcus mutans GS5 glucosyltransferase activities (both water-soluble and -insoluble glucan-synthesizing fractions) were inhibited by purified lipoteichoic acid. In vitro sucrose-dependent colonization of smooth surfaces by strain GS5 was also markedly reduced in the presence of the amphipathic molecules. The inhibition of soluble glucan synthesis by lipoteichoic acid appeared to be competitive with respect to both sucrose and primer dextran T10. These inhibitory effects were dependent on the presence of the fatty acid components of lipoteichoic acid since deacylated lipoteichoic acids did not inhibit glucosyltransferase activity. However, the deacylated molecules did interact with the enzymes since deacylated lipoteichoic acid partially protected the enzyme activity against heat inactivation and also induced the formation of high-molecular-weight enzyme complexes from the soluble glucan-synthesizing fraction. The presence of teichoic acid in high-molecular-weight aggregates of glucosyltransferase isolated from the culture fluids of strain GS5 was suggested by the detection of polyglycerophosphate in these fractions. In addition to strain GS5, two other organisms containing polyglycerophosphate teichoic acids, Lactobacillus casei and Lactobacillus fermentum , were demonstrated to bind glucosyltransferase activity. These results are discussed relative to the potential role of teichoic acid-glucosyltransferase interactions in enzyme binding to the cell surface of S. mutans and the formation of high-molecular-weight enzyme aggregates in the culture fluids of the organism.

scholarly journals Late Protective Effect of Netrin-1 in the Murine Acetaminophen Hepatotoxicity Model

2020 ◽  
Vol 175 (2) ◽  
pp. 168-181 ◽  
Author(s):  
Luqi Duan ◽  
Benjamin L Woolbright ◽  
Hartmut Jaeschke ◽  
Anup Ramachandran
Keyword(s):  
Liver Injury ◽  
Alanine Aminotransferase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Clinical Problem ◽  
The United States ◽  
Therapeutic Window ◽  
Protective Effects ◽  
Apap Overdose ◽  
Important Clinical Problem

Abstract Acetaminophen (APAP) overdose-induced acute liver failure is an important clinical problem in the United States and the current antidote N-acetylcysteine, has a short early therapeutic window. Since most patients present late to the clinic, there is need for novel late-acting therapeutic options. Though the neuronal guidance cue netrin-1, has been shown to promote hepatic repair and regeneration during liver ischemia/reperfusion injury, its effect in APAP-induced hepatotoxicity is unknown. In the quest for a late-acting therapeutic intervention in APAP-induced liver injury, we examined the role of netrin-1 in a mouse model of APAP overdose. Male C57BL/6J mice were cotreated with exogenous netrin-1 or vehicle control, along with 300 mg/kg APAP and euthanized at 6, 12, and 24 h. Significant elevations in alanine aminotransferase indicative of liver injury were seen in control mice at 6 h and this was not affected by netrin-1 administration. Also, netrin-1 treatment did not influence mitochondrial translocation of phospho-JNK, or peroxynitrite formation indicating that there was no interference with APAP-induced injury processes. Interestingly however, netrin-1 administration attenuated liver injury at 24 h, as seen by alanine aminotransferase levels and histology, at which time significant elevations in the netrin-1 receptor, adenosine A2B receptor (A2BAR) as well as macrophage infiltration was evident. Removal of resident macrophages with clodronate liposomes or treatment with the A2BAR antagonist PSB1115 blocked the protective effects of netrin-1. Thus, our data indicate a previously unrecognized role for netrin-1 in attenuation of APAP hepatotoxicity by enhancing recovery and regeneration, which is mediated through the A2BAR and involves resident liver macrophages.

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