title: Pretreatment of hepatocyte growth factor gene transfer mediated by octaarginine peptide-modified nanoparticles ameliorates LPS/D-galactosamine-induced hepatitis.
abstract: We previously reported that an octaarginine- and pH-sensitive fusogenic peptide-modified multifunctional envelope-type nano device (R8-GALA-MEND) produces a high level of gene expression in the liver. In this study, we report on an examination of whether this gene delivery system exerts potent hepatoprotective effects against lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute liver injury. In vivo-jetPEI(™)-Gal, a commercially available in vivo transfection reagent, was used as a reference. The systemic administration of the R8-GALA-MEND or in vivo-jetPEI(™)-Gal showed that the latter was more toxic than the R8-GALA-MEND, indicating that R8-GALA-MEND is a safer system than in vivo-jetPEI(™)-Gal. Pretreatment with R8-GALA-MEND or in vivo-jetPEI(™)-Gal loaded with hepatocyte growth factor (HGF) pDNA inhibited serum GPT and GOT levels from becoming elevated. However, the survival rate of the mice was significantly enhanced in the case of R8-GALA-MEND, but not for the in vivo-jetPEI(™)-Gal treatment. These results demonstrate that R8-GALA-MEND has the potential for use in the pretreatment of an acute liver injury.
authors.affiliation: Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Mizuno
authors.forename: Khalil A
authors.initials: KA
authors.lastname: Ikramy
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Akita
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D005688:Galactosamine; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy; D006505:Hepatitis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D049409:Luciferases, Firefly / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D010957:Plasmids; D014162:Transfection
chemical_list: D008070:Lipopolysaccharides; D009842:Oligopeptides; D010455:Peptides; C500307:octa-arginine peptide; C066951:GALA peptide; D017228:Hepatocyte Growth Factor; D005688:Galactosamine; D049409:Luciferases, Firefly; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase