Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 7, 2011; 17(1): 111-117
Published online Jan 7, 2011. doi: 10.3748/wjg.v17.i1.111
Protection of the liver against CCl4-induced injury by intramuscular electrotransfer of a kallistatin-encoding plasmid
Yong Diao, Xiao-Feng Zhao, Jun-Sheng Lin, Qi-Zhao Wang, Rui-An Xu
Yong Diao, Xiao-Feng Zhao, Qi-Zhao Wang, Rui-An Xu, Institute of Molecular Medicine, Huaqiao University, Quanzhou 362021, Fujian Province, China
Jun-Sheng Lin, Centre for Reproduction and Genomics, AgResearch, Invermay, Mosgiel 9053, New Zealand
Author contributions: Diao Y, Zhao XF and Wang QZ performed the majority of experiments; Lin JS provided analytical tools and was also involved in editing the manuscript; Diao Y and Xu RA designed the study and wrote the manuscript.
Supported by The State High Technology Research and Development Program of China (863 Program), No. 2008AA02Z135; the Important National Science and Technology Specific Projects, No. 2009ZX09103-643; and the Natural Science Foundation of China, No. 30973591
Correspondence to: Yong Diao, Professor, Institute of Molecular Medicine, Huaqiao University, Quanzhou 362021, Fujian Province, China. diaoyong@hqu.edu.cn
Telephone: +86-595-22692516 Fax: +86-595-22690516
Received: July 9, 2010
Revised: October 16, 2010
Accepted: October 23, 2010
Published online: January 7, 2011
Abstract

AIM: To investigate the effect of transgenic expression of kallistatin (Kal) on carbon tetrachloride (CCl4)-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.

CONCLUSION: 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.

Keywords: Kallistatin, Gene delivery systems, Electroporation, Drug formulation, Liver injury