title: Protection of the liver against CCl4-induced injury by intramuscular electrotransfer of a kallistatin-encoding plasmid.
abstract: OBJECTIVE
  To investigate the effect of transgenic expression of kallistatin (Kal) on carbon tetrachloride (CCl(4))-induced liver injury by intramuscular (im) electrotransfer of a Kal-encoding plasmid formulated with poly-L-glutamate (PLG).
  
  
  METHODS
  The pKal plasmid encoding Kal gene was formulated with PLG and electrotransferred into mice skeletal muscle before the administration of CCl4. The expression level of Kal was measured. The serum biomarker levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malonyldialdehyde (MDA), and tumor necrosis factor (TNF)-α were monitored. The extent of CCl4-induced liver injury was analyzed histopathologically.
  
  
  RESULTS
  The transgene of Kal was sufficiently expressed after an im injection of plasmid formulated with PLG followed by electroporation. In the Kal gene-transferred mice, protection against CCl4-induced liver injury was reflected by significantly decreased serum ALT, AST, MDA and TNF-α levels compared to those in control mice (P<0.01 to 0.05 in a dose-dependent manner). Histological observations also revealed that hepatocyte necrosis, hemorrhage, vacuolar change and hydropic degeneration were apparent in mice after CCl4 administration. In contrast, the damage was markedly attenuated in the Kal gene-transferred mice. The expression of hepatic fibrogenesis marker transforming growth factor-β1 was also reduced in the pKal transferred mice.
  
  
  CONCLUSIONS
  Intramuscular electrotransfer of plasmid pKal which was formulated with PLG significantly alleviated the CCl4-induced oxidative stress and inflammatory response, and reduced the liver damage in a mouse model.
authors.affiliation: Institute of Molecular Medicine, Huaqiao University, Quanzhou 362021, Fujian Province, China. diaoyong@hqu.edu.cn
authors.forename: Yong
authors.initials: Y
authors.lastname: Diao
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Zhao
authors.forename: Jun-Sheng
authors.initials: JS
authors.lastname: Lin
authors.forename: Qi-Zhao
authors.initials: QZ
authors.lastname: Wang
authors.forename: Rui-An
authors.initials: RA
authors.lastname: Xu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology; D018274:Electroporation / Q000379:methods*; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D008099:Liver / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology; D010957:Plasmids / Q000235:genetics / Q000378:metabolism*; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D015843:Serpins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C051324:kallistatin; D002251:Carbon Tetrachloride