Intrahepatic Delivery of Pegylated Catalase Is Protective in a Rat Ischemia/Reperfusion Injury Model

Ischemia/reperfusion injury (IRI) can occur during liver surgery. Endogenous catalase is important to cellular antioxidant defenses and is critical to IRI prevention. Pegylation of catalase (PEG-CAT) improves its therapeutic potential by extending plasma half-life, but systemic administration of exo...

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Bibliographic Details
Published in:The Journal of surgical research 2019-06, Vol.238, p.152-163
Main Authors: Akateh, Clifford, Beal, Eliza W., Kim, Jung-Lye, Reader, Brenda F., Maynard, Katelyn, Zweier, Jay L., Whitson, Bryan A., Black, Sylvester M.
Format: Article
Language:English
Subjects:
Alanine Transaminase - blood
Animals
Aspartate Aminotransferases - blood
Catalase - administration & dosage
Cell Survival - drug effects
Disease Models, Animal
Hepatectomy
Humans
Hydrogen peroxide
Hydrogen Peroxide - pharmacology
Injections, Intralesional
Ischemia/reperfusion injury
Liver - blood supply
Liver - cytology
Liver - surgery
Liver transplantation
Male
Oxidative stress
Oxidative Stress - drug effects
PEG-CAT
PEGylated catalase
Polyethylene Glycols - administration & dosage
Primary Cell Culture
Rats
Reperfusion Injury - blood
Reperfusion Injury - drug therapy
Reperfusion Injury - etiology
Treatment Outcome
Warm Ischemia - adverse effects
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Summary:Ischemia/reperfusion injury (IRI) can occur during liver surgery. Endogenous catalase is important to cellular antioxidant defenses and is critical to IRI prevention. Pegylation of catalase (PEG-CAT) improves its therapeutic potential by extending plasma half-life, but systemic administration of exogenous PEG-CAT has been only mildly therapeutic for hepatic IRI. Here, we investigated the protective effects of direct intrahepatic delivery of PEG-CAT during IRI using a rat hilar clamp model. PEG-CAT was tested in vitro and in vivo. In vitro, enriched rat liver cell populations were subjected to oxidative stress injury (H2O2), and measures of cell health and viability were assessed. In vivo, rats underwent segmental (70%) hepatic warm ischemia for 1 h, followed by 6 h of reperfusion, and plasma alanine aminotransferase and aspartate aminotransferase, tissue malondialdehyde, adenosine triphosphate, and GSH, and histology were assessed. In vitro, PEG-CAT pretreatment of liver cells showed substantial uptake and protection against oxidative stress injury. In vivo, direct intrahepatic, but not systemic, delivery of PEG-CAT during IRI significantly reduced alanine aminotransferase and aspartate aminotransferase in a time-dependent manner (P 
ISSN:0022-4804
1095-8673
DOI:10.1016/j.jss.2019.01.028