scholarly journals Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach

2021 ◽  
Vol 22 (10) ◽  
pp. 5332
Author(s):  
Raquel G. Bardallo ◽  
Rui Teixeira da Silva ◽  
Teresa Carbonell ◽  
Emma Folch-Puy ◽  
Carlos Palmeira ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fatty Liver ◽  
Liver Graft ◽  
Suitable Alternative ◽  
Graft Preservation ◽  
Preservation Solutions ◽  
Microcirculatory Disturbances ◽  
Organ Recovery ◽  
Surgical Manipulations

The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.

scholarly journals Role of nitric oxide in hepatic microvascular injury elicited by acetaminophen in mice

2004 ◽  
Vol 286 (1) ◽  
pp. G60-G67 ◽  
Author(s):  
Yoshiya Ito ◽  
Edward R. Abril ◽  
Nancy W. Bethea ◽  
Robert S. McCuskey
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Cell Injury ◽  
Parenchymal Cell ◽  
Protective Role ◽  
Hepatic Expression ◽  
Inos Inhibitor ◽  
Microcirculatory Disturbances

Nitric oxide (NO) is suggested to play a role in liver injury elicited by acetaminophen (APAP). Hepatic microcirculatory dysfunction also is reported to contribute to the development of the injury. As a result, the role of NO in hepatic microcirculatory alterations in response to APAP was examined in mice by in vivo microscopy. A selective inducible NO synthase (iNOS) inhibitor,l- N6-(1-iminoethyl)-lysine (l-NIL), or a nonselective NOS inhibitor, NG-nitro-l-arginine methyl ester (l-NAME), was intraperitoneally administered to animals 10 min before APAP gavage. l-NIL suppressed raised alanine aminotransferase (ALT) values 6 h after APAP, whereas l-NAME increased those 1.7-fold. Increased ALT levels were associated with hepatic expression of iNOS. l-NIL, but not l-NAME, reduced the expression. APAP caused a reduction (20%) in the numbers of perfused sinusoids. l-NIL restored the sinusoidal perfusion, but l-NAME was ineffective. APAP increased the area occupied by infiltrated erythrocytes into the extrasinusoidal space. l-NIL tended to minimize this infiltration, whereas l-NAME further enhanced it. APAP caused an increase (1.5-fold) in Kupffer cell phagocytic activity. This activity in response to APAP was blunted by l-NIL, whereas l-NAME further elevated it. l-NIL suppressed APAP-induced decreases in hepatic glutathione levels. These results suggest that NO derived from iNOS contributes to APAP-induced parenchymal cell injury and hepatic microcirculatory disturbances. l-NIL exerts preventive effects on the liver injury partly by inhibiting APAP bioactivation. In contrast, NO derived from constitutive isoforms of NOS exerts a protective role in liver microcirculation against APAP intoxication and thereby minimizes liver injury.

AMPK involvement in endoplasmic reticulum stress and autophagy modulation after fatty liver graft preservation: a role for melatonin and trimetazidine cocktail

2013 ◽  
Vol 55 (1) ◽  
pp. 65-78 ◽  
Author(s):  
Mohamed Amine Zaouali ◽  
Eleonora Boncompagni ◽  
Russel J. Reiter ◽  
Mohamed Bejaoui ◽  
Isabel Freitas ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Fatty Liver ◽  
Liver Graft ◽  
Graft Preservation

scholarly journals Relevance of proteolysis and proteasome activation in fatty liver graft preservation: An Institut Georges Lopez-1vsUniversity of Wisconsin appraisal

2017 ◽  
Vol 23 (23) ◽  
pp. 4211 ◽  
Author(s):  
Mohamed Amine Zaouali ◽  
Arnau Panisello-Roselló ◽  
Alexandre Lopez ◽  
Carlos Castro Benítez ◽  
Emma Folch-Puy ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Liver Graft ◽  
Graft Preservation

scholarly journals PEG35 and Glutathione Improve Mitochondrial Function and Reduce Oxidative Stress in Cold Fatty Liver Graft Preservation

Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 158
Author(s):  
Raquel G. Bardallo ◽  
Idoia Company-Marin ◽  
Emma Folch-Puy ◽  
Joan Roselló-Catafau ◽  
Arnau Panisello-Rosello ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Liver ◽  
Uncoupling Protein ◽  
Ischemia Reperfusion ◽  
Liver Graft ◽  
Zucker Rats ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Atp Production ◽  
Preservation Solutions

The need to meet the demand for transplants entails the use of steatotic livers, more vulnerable to ischemia-reperfusion (IR) injury. Therefore, finding the optimal composition of static cold storage (SCS) preservation solutions is crucial. Given that ROS regulation is a therapeutic strategy for liver IR injury, we have added increasing concentrations of PEG35 and glutathione (GSH) to the preservation solutions (IGL-1 and IGL-2) and evaluated the possible protection against energy depletion and oxidative stress. Fatty livers from obese Zücker rats were isolated and randomly distributed in the control (Sham) preserved (24 h at 4 °C) in IGL-0 (without PEG35 and 3 mmol/L GSH), IGL-1 (1 g/L PEG35, and 3 mmol/L GSH), and IGL-2 (5 g/L PEG35 and 9 mmol/L GSH). Energy metabolites (ATP and succinate) and the expression of mitochondrial oxidative phosphorylation complexes (OXPHOS) were determined. Mitochondrial carrier uncoupling protein 2 (UCP2), PTEN-induced kinase 1 (PINK1), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and the inflammasome (NLRP3) expressions were analyzed. As biomarkers of oxidative stress, protein oxidation (AOPP) and carbonylation (DNP derivatives), and lipid peroxidation (malondialdehyde (MDA)–thiobarbituric acid (TBA) adducts) were measured. In addition, the reduced and oxidized glutathione (GSH and GSSG) and enzymatic (Cu–Zn superoxide dismutase (SOD), CAT, GSH S-T, GSH-Px, and GSH-R) antioxidant capacities were determined. Our results showed that the cold preservation of fatty liver graft depleted ATP, accumulated succinate and increased oxidative stress. In contrast, the preservation with IGL-2 solution maintained ATP production, decreased succinate levels and increased OXPHOS complexes I and II, UCP2, and PINK-1 expression, therefore maintaining mitochondrial integrity. IGL-2 also protected against oxidative stress by increasing Nrf2 and HO-1 expression and GSH levels. Therefore, the presence of PEG35 in storage solutions may be a valuable option as an antioxidant agent for organ preservation in clinical transplantation.

Comparative prospective study of two liver graft preservation solutions: University of Wisconsin and Celsior

2009 ◽  
Vol 15 (12) ◽  
pp. 1709-1717 ◽  
Author(s):  
Rafael Lopez-Andujar ◽  
Saulo Deusa ◽  
Eva Montalvá ◽  
Fernando San Juan ◽  
Angel Moya ◽  
...  
Keyword(s):  
Prospective Study ◽  
Liver Graft ◽  
University Of Wisconsin ◽  
Graft Preservation ◽  
Preservation Solutions ◽  
Comparative Prospective Study

Machine perfusion at 20°C as valid alternative for fatty liver graft preservation

2007 ◽  
Vol 39 (10) ◽  
pp. A37 ◽  
Author(s):  
E. Boncompagni ◽  
C. Guarnaschelli ◽  
V. Bertone ◽  
A. Ferrigno ◽  
F. Carlucci ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Liver Graft ◽  
Machine Perfusion ◽  
Graft Preservation

HIF IS UNDER CONTROL OF NITRIC OXIDE IN NORMOXIC FATTY LIVER GRAFT REPERFUSION INJURY

2010 ◽  
Vol 90 ◽  
pp. 843
Author(s):  
M. A. Zaouali ◽  
E. Boncompagni ◽  
H. Ben Abdennebi ◽  
J. Viñas ◽  
I. Freitas ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fatty Liver ◽  
Reperfusion Injury ◽  
Liver Graft

scholarly journals The association between acute fatty liver disease and nitric oxide during malaria in pregnancy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mamoru Niikura ◽  
Toshiyuki Fukutomi ◽  
Shoichiro Mineo ◽  
Jiro Mitobe ◽  
Fumie Kobayashi
Keyword(s):  
Nitric Oxide ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Infiltration ◽  
Malaria In Pregnancy ◽  
Pregnant Mice ◽  
Acute Fatty Liver ◽  
Ifn Γ ◽  
In Pregnancy

Abstract Background Liver disease is a common feature of malaria in pregnancy, but its pathogenesis remains unclear. Methods To understand the pathogenesis of liver disease during malaria in pregnancy, comparative proteomic analysis of the liver in a mouse model of malaria in pregnancy was performed. Results Decreased levels of mitochondrial and peroxisomal proteins were observed in the livers of pregnant mice infected with the lethal rodent malaria parasite Plasmodium berghei strain NK65. By contrast, increased levels of perilipin-2, amyloid A-1, and interferon (IFN)-γ signalling pathway-related proteins were observed in the livers of infected pregnant mice, suggesting that IFN-γ signalling may contribute to the development of liver disease during malaria in pregnancy. IFN-γ signalling is a potential trigger of inducible nitric oxide synthase (iNOS) expression. Liver disease associated with microvesicular fatty infiltration and elevated liver enzymes in pregnant wild-type mice infected with malaria parasites was improved by iNOS deficiency. Conclusions In this study, a causative role of iNOS in liver disease associated with microvesicular fatty infiltration during malaria in pregnancy was demonstrated. These findings provide important insight for understanding the role of iNOS-mediated metabolic responses and the pathogenesis of high-risk liver diseases in pregnancy, such as acute fatty liver.

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