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Transgene expression of human PON1 Q in mice protected the liver against CCl 4 ‐induced injury
Author(s) -
Zhang Chi,
Peng Wei,
Jiang Xiaoling,
Chen Bo,
Zhu Jie,
Zang Yuhui,
Zhang Junfeng,
Zhu Tongyang,
Qin Junchuan
Publication year - 2008
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.1128
Subject(s) - pon1 , liver injury , transgene , oxidative stress , paraoxonase , lipid peroxidation , genetically modified mouse , antioxidant , hepatocyte , medicine , endocrinology , pharmacology , biology , immunology , gene , biochemistry , genotype , in vitro
Background Oxidative stress, often in association with decreased antioxidant defenses, plays a pathogenetic role in both initiation and progression of liver injuries, leading to almost all clinical and experimental conditions of chronic liver diseases. Human paraoxonase 1 (hPON1) is a liver‐synthesized enzyme possessing antioxidant properties. Here, we investigate the effects of transgene‐expressed hPON1 Q on alleviating lipid peroxidation and preventing liver injury in a mouse model. Methods The hPON1 Q gene was cloned into pcDNA3.0 plasmid and electro‐transferred into mouse skeletal muscle. After CCl 4 had been administrated to induce liver injury, mice were monitored for serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and malonyldialdehyde (MDA). The extent of CCl 4 ‐induced liver injury was also analyzed through histopathological observations. Results After gene delivery, hPON1 mRNA expression was detected in mouse muscle and serum PON1 activity was 1.5 times higher than that of the control counterpart. In the PON1 Q gene transferred mice, protection against CCl 4 ‐induced liver injury was reflected by significantly decreased serum ALT, AST and MDA levels compared to those in control mice ( P < 0.01). Histological observations also revealed that hepatocyte necrosis, hemorrhage, vacuolar change and hydropic degeneration were apparent in control mice after CCl 4 administration. In contrast, the damage was significantly prevented ( P < 0.01) in the hPON1 Q transferred mice. Conclusions Intramuscular electro‐transfer of the hPON1 Q gene led to efficient expression of hPON1 in mice. Elevated levels of PON1, by virtue of its potency to alleviate oxidative stress, could protect mice from suffering CCl 4 ‐induced liver damage. Copyright © 2007 John Wiley & Sons, Ltd.