Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice

Song Qing He, Yan Hong Zhang, Senthil K. Venugopal, Christopher W. Dicus, Richard V Perez, Rajen Ramsamooj, Michael H. Nantz, Mark A Zern, Jian Wu

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Hepatic ischemia/reperfusion (I/R) injury is characterized by the generation of reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide. The aim of this study is to investigate whether antioxidative gene delivery by our polylipid nanoparticles (PLNP) is an effective approach for prevention of the injury. Polyplexes of extracellular superoxide dismutase (EC-SOD) and/or catalase genes were injected via the portal vein 1 day prior to a warm I/R procedure in mice. The effects of the gene delivery were determined 6 hours after starting reperfusion. PLNP-mediated antioxidative gene delivery led to a marked increase in human EC-SOD and catalase gene expression in the liver. Liver superoxide dismutase (SOD) and catalase activity both increased approximately 10-fold. Increased liver superoxide anion levels caused by the I/R procedure were reduced to normal levels by EC-SOD gene delivery. The overexpression of these 2 antioxidative genes significantly suppressed the I/R-induced elevation of serum alanine aminotransferase (ALT) levels, decreased liver malondialdehyde content, restored glutathione reserve, and improved liver histology. In conclusion, EC-SOD or catalase gene delivery by PLNP resulted in high levels of the transgene activity in the liver, and markedly attenuated hepatic I/R injury. The protection is directly associated with elevated antioxidative enzyme activity as the result of the gene delivery. This novel approach may become a potential therapy to improve graft function and survival after liver transplantation.

Original languageEnglish (US)
Pages (from-to)1869-1879
Number of pages11
JournalLiver Transplantation
Volume12
Issue number12
DOIs
StatePublished - Dec 2006

Fingerprint

Reperfusion
Ischemia
Superoxide Dismutase
Liver
Wounds and Injuries
Enzymes
Catalase
Genes
Nanoparticles
Reperfusion Injury
Superoxides
Warm Ischemia
Graft Survival
Portal Vein
Malondialdehyde
Alanine Transaminase
Transgenes
Liver Transplantation
Hydrogen Peroxide
Glutathione

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice. / He, Song Qing; Zhang, Yan Hong; Venugopal, Senthil K.; Dicus, Christopher W.; Perez, Richard V; Ramsamooj, Rajen; Nantz, Michael H.; Zern, Mark A; Wu, Jian.

In: Liver Transplantation, Vol. 12, No. 12, 12.2006, p. 1869-1879.

Research output: Contribution to journalArticle

He, SQ, Zhang, YH, Venugopal, SK, Dicus, CW, Perez, RV, Ramsamooj, R, Nantz, MH, Zern, MA & Wu, J 2006, 'Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice', Liver Transplantation, vol. 12, no. 12, pp. 1869-1879. https://doi.org/10.1002/lt.21001
He, Song Qing ; Zhang, Yan Hong ; Venugopal, Senthil K. ; Dicus, Christopher W. ; Perez, Richard V ; Ramsamooj, Rajen ; Nantz, Michael H. ; Zern, Mark A ; Wu, Jian. / Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice. In: Liver Transplantation. 2006 ; Vol. 12, No. 12. pp. 1869-1879.
@article{970cae68ed7744d4a5fac4f6d92eadc9,
title = "Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice",
abstract = "Hepatic ischemia/reperfusion (I/R) injury is characterized by the generation of reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide. The aim of this study is to investigate whether antioxidative gene delivery by our polylipid nanoparticles (PLNP) is an effective approach for prevention of the injury. Polyplexes of extracellular superoxide dismutase (EC-SOD) and/or catalase genes were injected via the portal vein 1 day prior to a warm I/R procedure in mice. The effects of the gene delivery were determined 6 hours after starting reperfusion. PLNP-mediated antioxidative gene delivery led to a marked increase in human EC-SOD and catalase gene expression in the liver. Liver superoxide dismutase (SOD) and catalase activity both increased approximately 10-fold. Increased liver superoxide anion levels caused by the I/R procedure were reduced to normal levels by EC-SOD gene delivery. The overexpression of these 2 antioxidative genes significantly suppressed the I/R-induced elevation of serum alanine aminotransferase (ALT) levels, decreased liver malondialdehyde content, restored glutathione reserve, and improved liver histology. In conclusion, EC-SOD or catalase gene delivery by PLNP resulted in high levels of the transgene activity in the liver, and markedly attenuated hepatic I/R injury. The protection is directly associated with elevated antioxidative enzyme activity as the result of the gene delivery. This novel approach may become a potential therapy to improve graft function and survival after liver transplantation.",
author = "He, {Song Qing} and Zhang, {Yan Hong} and Venugopal, {Senthil K.} and Dicus, {Christopher W.} and Perez, {Richard V} and Rajen Ramsamooj and Nantz, {Michael H.} and Zern, {Mark A} and Jian Wu",
year = "2006",
month = "12",
doi = "10.1002/lt.21001",
language = "English (US)",
volume = "12",
pages = "1869--1879",
journal = "Liver Transplantation",
issn = "1527-6465",
publisher = "John Wiley and Sons Ltd",
number = "12",

}

TY - JOUR

T1 - Delivery of antioxidative enzyme genes protects against ischemia/reperfusion-induced liver injury in mice

AU - He, Song Qing

AU - Zhang, Yan Hong

AU - Venugopal, Senthil K.

AU - Dicus, Christopher W.

AU - Perez, Richard V

AU - Ramsamooj, Rajen

AU - Nantz, Michael H.

AU - Zern, Mark A

AU - Wu, Jian

PY - 2006/12

Y1 - 2006/12

N2 - Hepatic ischemia/reperfusion (I/R) injury is characterized by the generation of reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide. The aim of this study is to investigate whether antioxidative gene delivery by our polylipid nanoparticles (PLNP) is an effective approach for prevention of the injury. Polyplexes of extracellular superoxide dismutase (EC-SOD) and/or catalase genes were injected via the portal vein 1 day prior to a warm I/R procedure in mice. The effects of the gene delivery were determined 6 hours after starting reperfusion. PLNP-mediated antioxidative gene delivery led to a marked increase in human EC-SOD and catalase gene expression in the liver. Liver superoxide dismutase (SOD) and catalase activity both increased approximately 10-fold. Increased liver superoxide anion levels caused by the I/R procedure were reduced to normal levels by EC-SOD gene delivery. The overexpression of these 2 antioxidative genes significantly suppressed the I/R-induced elevation of serum alanine aminotransferase (ALT) levels, decreased liver malondialdehyde content, restored glutathione reserve, and improved liver histology. In conclusion, EC-SOD or catalase gene delivery by PLNP resulted in high levels of the transgene activity in the liver, and markedly attenuated hepatic I/R injury. The protection is directly associated with elevated antioxidative enzyme activity as the result of the gene delivery. This novel approach may become a potential therapy to improve graft function and survival after liver transplantation.

AB - Hepatic ischemia/reperfusion (I/R) injury is characterized by the generation of reactive oxygen species (ROS), such as superoxide anions and hydrogen peroxide. The aim of this study is to investigate whether antioxidative gene delivery by our polylipid nanoparticles (PLNP) is an effective approach for prevention of the injury. Polyplexes of extracellular superoxide dismutase (EC-SOD) and/or catalase genes were injected via the portal vein 1 day prior to a warm I/R procedure in mice. The effects of the gene delivery were determined 6 hours after starting reperfusion. PLNP-mediated antioxidative gene delivery led to a marked increase in human EC-SOD and catalase gene expression in the liver. Liver superoxide dismutase (SOD) and catalase activity both increased approximately 10-fold. Increased liver superoxide anion levels caused by the I/R procedure were reduced to normal levels by EC-SOD gene delivery. The overexpression of these 2 antioxidative genes significantly suppressed the I/R-induced elevation of serum alanine aminotransferase (ALT) levels, decreased liver malondialdehyde content, restored glutathione reserve, and improved liver histology. In conclusion, EC-SOD or catalase gene delivery by PLNP resulted in high levels of the transgene activity in the liver, and markedly attenuated hepatic I/R injury. The protection is directly associated with elevated antioxidative enzyme activity as the result of the gene delivery. This novel approach may become a potential therapy to improve graft function and survival after liver transplantation.

UR - http://www.scopus.com/inward/record.url?scp=33845472283&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845472283&partnerID=8YFLogxK

U2 - 10.1002/lt.21001

DO - 10.1002/lt.21001

M3 - Article

C2 - 17133584

AN - SCOPUS:33845472283

VL - 12

SP - 1869

EP - 1879

JO - Liver Transplantation

JF - Liver Transplantation

SN - 1527-6465

IS - 12

ER -