Protection of the Liver Against CCl4-induced Injury by Intramuscular Electrotransfer of a Kallistatin-encoding Plasmid

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2011 Jan 11

PMID 21218091

Citations 18

Authors

Yong Diao

Xiao-Feng Zhao

Jun-Sheng Lin

Qi-Zhao Wang

Rui-An Xu

Affiliations

Soon will be listed here.

Abstract

Aim: 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.

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.

Citing Articles

A study of the hepatoprotective effect of Plantago psyllium L. seed extract against Carbon tetrachloride induced hepatic injury in rats.

Abouzied M, Mahmoud S, Wahid A, Ahmed A, Okasha A, Soliman H J Appl Biomed. 2021; 18(2-3):80-86.

PMID: 34907729 DOI: 10.32725/jab.2020.006.

Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis.

Krishna S, Li J, Wang Y, Moran C, Trollope A, Huynh P Sci Rep. 2021; 11(1):17451.

PMID: 34465809 PMC: 8408144. DOI: 10.1038/s41598-021-97042-8.

Hepatoprotective effect of crude polysaccharides extracted from against carbon tetrachloride-induced liver injury in mice.

Susilo R, Winarni D, Husen S, Hayaza S, Punnapayak H, Wahyuningsih S Vet World. 2020; 12(12):1987-1991.

PMID: 32095051 PMC: 6989327. DOI: 10.14202/vetworld.2019.1987-1991.

Regression of fibrosis by cilostazol in a rat model of thioacetamide-induced liver fibrosis: Up regulation of hepatic cAMP, and modulation of inflammatory, oxidative stress and apoptotic biomarkers.

Awdan S, Abdel Rahman R, Ibrahim H, Hegazy R, El Marasy S, Badawi M PLoS One. 2019; 14(5):e0216301.

PMID: 31067255 PMC: 6505801. DOI: 10.1371/journal.pone.0216301.

Hepatoprotective and antioxidant effects of single clove garlic against CCl-induced hepatic damage in rabbits.

Naji K, Al-Shaibani E, Alhadi F, Al-Soudi S, Dsouza M BMC Complement Altern Med. 2017; 17(1):411.

PMID: 28818066 PMC: 5561638. DOI: 10.1186/s12906-017-1916-8.

References

Chao J, Yin H, Yao Y, Shen B, Smith Jr R, Chao L . Novel role of kallistatin in protection against myocardial ischemia-reperfusion injury by preventing apoptosis and inflammation. Hum Gene Ther. 2006; 17(12):1201-13. DOI: 10.1089/hum.2006.17.1201. View

Shen B, Hagiwara M, Yao Y, Chao L, Chao J . Salutary effect of kallistatin in salt-induced renal injury, inflammation, and fibrosis via antioxidative stress. Hypertension. 2008; 51(5):1358-65. DOI: 10.1161/HYPERTENSIONAHA.107.108514. View

Tunon M, Alvarez M, Culebras J, Gonzalez-Gallego J . An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure. World J Gastroenterol. 2009; 15(25):3086-98. PMC: 2705730. DOI: 10.3748/wjg.15.3086. View

Fewell J, MacLaughlin F, Mehta V, Gondo M, Nicol F, Wilson E . Gene therapy for the treatment of hemophilia B using PINC-formulated plasmid delivered to muscle with electroporation. Mol Ther. 2001; 3(4):574-83. DOI: 10.1006/mthe.2001.0295. View

Hui S . Overview of drug delivery and alternative methods to electroporation. Methods Mol Biol. 2008; 423:91-107. DOI: 10.1007/978-1-59745-194-9_6. View

Bloquel C, Fabre E, Bureau M, Scherman D . Plasmid DNA electrotransfer for intracellular and secreted proteins expression: new methodological developments and applications. J Gene Med. 2004; 6 Suppl 1:S11-23. DOI: 10.1002/jgm.508. View

Sersa G, Miklavcic D, Cemazar M, Rudolf Z, Pucihar G, Snoj M . Electrochemotherapy in treatment of tumours. Eur J Surg Oncol. 2007; 34(2):232-40. DOI: 10.1016/j.ejso.2007.05.016. View

Andre F, Gehl J, Sersa G, Preat V, Hojman P, Eriksen J . Efficiency of high- and low-voltage pulse combinations for gene electrotransfer in muscle, liver, tumor, and skin. Hum Gene Ther. 2009; 19(11):1261-71. DOI: 10.1089/hum.2008.060. View

Daud A, DeConti R, Andrews S, Urbas P, Riker A, Sondak V . Phase I trial of interleukin-12 plasmid electroporation in patients with metastatic melanoma. J Clin Oncol. 2008; 26(36):5896-903. PMC: 2645111. DOI: 10.1200/JCO.2007.15.6794. View

10.

Gao L, Yin H, Smith Jr R, Chao L, Chao J . Role of kallistatin in prevention of cardiac remodeling after chronic myocardial infarction. Lab Invest. 2008; 88(11):1157-66. DOI: 10.1038/labinvest.2008.85. View

11.

Xu R, Harrison P, Chen M, Li L, Tsui T, Fung P . Cytoglobin overexpression protects against damage-induced fibrosis. Mol Ther. 2006; 13(6):1093-100. DOI: 10.1016/j.ymthe.2005.11.027. View

12.

de Meijer V, Sverdlov D, Popov Y, Le H, Meisel J, Nose V . Broad-spectrum matrix metalloproteinase inhibition curbs inflammation and liver injury but aggravates experimental liver fibrosis in mice. PLoS One. 2010; 5(6):e11256. PMC: 2892485. DOI: 10.1371/journal.pone.0011256. View

13.

Diao Y, Ma J, Xiao W, Luo J, Li X, Chu K . Inhibition of angiogenesis and HCT-116 xenograft tumor growth in mice by kallistatin. World J Gastroenterol. 2007; 13(34):4615-9. PMC: 4611838. DOI: 10.3748/wjg.v13.i34.4615. View

14.

Mir L, Bureau M, Gehl J, Rangara R, Rouy D, CAILLAUD J . High-efficiency gene transfer into skeletal muscle mediated by electric pulses. Proc Natl Acad Sci U S A. 1999; 96(8):4262-7. PMC: 16320. DOI: 10.1073/pnas.96.8.4262. View

15.

Miklavcic D, Snoj M, Zupanic A, Kos B, Cemazar M, Kropivnik M . Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. Biomed Eng Online. 2010; 9:10. PMC: 2843684. DOI: 10.1186/1475-925X-9-10. View

16.

Nicol F, Wong M, MacLaughlin F, Perrard J, Wilson E, Nordstrom J . Poly-L-glutamate, an anionic polymer, enhances transgene expression for plasmids delivered by intramuscular injection with in vivo electroporation. Gene Ther. 2002; 9(20):1351-8. DOI: 10.1038/sj.gt.3301806. View

17.

Testori A, Tosti G, Martinoli C, Spadola G, Cataldo F, Verrecchia F . Electrochemotherapy for cutaneous and subcutaneous tumor lesions: a novel therapeutic approach. Dermatol Ther. 2010; 23(6):651-61. DOI: 10.1111/j.1529-8019.2010.01370.x. View

18.

Cukjati D, Batiuskaite D, Andre F, Miklavcic D, Mir L . Real time electroporation control for accurate and safe in vivo non-viral gene therapy. Bioelectrochemistry. 2007; 70(2):501-7. DOI: 10.1016/j.bioelechem.2006.11.001. View

19.

Alberts B . The breakthroughs of 2009. Science. 2009; 326(5960):1589. DOI: 10.1126/science.1185821. View

20.

Wang C, Chen S, Wu C, Liu M, Jin Y, Chao L . Prophylactic adenovirus-mediated human kallistatin gene therapy suppresses rat arthritis by inhibiting angiogenesis and inflammation. Arthritis Rheum. 2005; 52(4):1319-24. DOI: 10.1002/art.20991. View