Polyethylene glycols: An effective strategy for limiting liver ischemia reperfusion injury.
Liver ischemia-reperfusion injury (IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ (ischemia) is exacerbated following the return of oxygen delivery (reperfusion). IRI is a major cause of primary non-function after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions (antioxidants, anti-cytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols (PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Gianfranco
G
Pasut
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Arnau
A
Panisello
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Emma
E
Folch-Puy
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Alexandre
A
Lopez
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Carlos
C
Castro-Benítez
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Maria
M
Calvo
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Teresa
T
Carbonell
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Agustín
A
García-Gil
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
René
R
Adam
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy.
Joan
J
Roselló-Catafau
D050377:Cold Ischemia; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D008107:Liver Diseases / Q000517:prevention & control*; D016031:Liver Transplantation / Q000379:methods*; D019188:Organ Preservation Solutions; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D055031:Primary Graft Dysfunction / Q000517:prevention & control*; D020011:Protective Agents / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000517:prevention & control*
D019188:Organ Preservation Solutions; D020011:Protective Agents; D011092:Polyethylene Glycols
IGL-1 solution; Ischemia reperfusion injury; Liver preconditioning; Liver transplantation; Machine perfusion; PEG rinse solution; Polyethylene glycol; SCOT solution; UW solution