Influence of Murine Hepatitis Induced by D-(+)-Galactosamine Hydrochloride and Lipopolysaccharide on Gene Expression of Polyethylenimine/plasmid DNA Polyplex

• Published in: Biological & Pharmaceutical Bulletin 2008/08/01, Vol.31(8), pp.1585-1589
• Main Authors: Miyanaga, Kei, Yoshioka, Takashi, Nakagawa, Hiroo, Kitahara, Takashi, To, Hideto, Ichikawa, Nobuhiro, Nakashima, Mikiro, Nishida, Koyo, Nakamura, Junzo, Sasaki, Hitoshi
• Format: Article
• Language: English
• Subjects: Animals; Chemical and Drug Induced Liver Injury - genetics; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; disease stage; DNA - administration & dosage; DNA - biosynthesis; Drug Delivery Systems; Excipients; Galactosamine; gene delivery; Gene Expression - drug effects; Gene Transfer Techniques; Genes, Reporter; Lipopolysaccharides; Liver - pathology; Liver Function Tests; Luciferases - genetics; Mice; murine hepatitis; non-viral vector; Plasmids - administration & dosage; Plasmids - biosynthesis; Polyethyleneimine; polyethylenimine; Tissue Distribution
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.31.1585

We investigated the influence of murine hepatitis induced by D-(+)-galactosamine and lipopolysaccharide (D-GalN/LPS) on polyethylenimine (PEI)-mediated plasmid DNA (pDNA) delivery. pDNA encoding firefly luciferase was used as the model reporter gene. PEI was used as the non-viral vector because of its high gene expression and low toxicity. The activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mice indicated the highest peaks at 12 h after D-GalN/LPS injection, then the activities of serum ALT and AST rapidly decreased. We determined luciferase activity in various organs of D-GalN/LPS-treated mice and control mice after an intravenous administration of PEI/pDNA complexes. High transgene expression was observed in the liver, spleen, and lung of both mice. Compared to the control mice, a significant increase of transgene expression was observed in the liver of D-GalN/LPS-treated mice after D-GalN/LPS injection. The transgene expression in the spleen and lung decreased at 6 and 12 h after D-GalN/LPS injection. In conclusion, we found that murine hepatitis induced by D-GalN/LPS injection can influence PEI-mediated pDNA delivery and its influence was different from that induced by CCl4 injection which was reported previously. These results demonstrated the necessity of considering the timing and dose of gene therapy according to the disease and its stage.