(melle-4)cyclosporin and Liver-Failure--Acute

(melle-4)cyclosporin has been researched along with Liver-Failure--Acute* in 1 studies

Other Studies

1 other study(ies) available for (melle-4)cyclosporin and Liver-Failure--Acute

Article	Year
Administration of naked plasmid encoding hepatic stimulator substance by hydrodynamic tail vein injection protects mice from hepatic failure by suppressing the mitochondrial permeability transition. The Journal of pharmacology and experimental therapeutics, 2011, Volume: 338, Issue:3 Acute liver failure is a devastating illness of various causes with considerable mortality. Hepatic stimulator substance (HSS) has been suggested for use as a protective agent against acute hepatic injury induced by chemical poisons because it has a variety of biological activities. However, the mechanism whereby HSS protects against hepatotoxins is poorly understood. In this study, we established a hepatic gene transfer system via hydrodynamic tail vein injection to deliver a naked plasmid containing the human HSS gene (hHSS) and analyzed HSS-mediated protection of the liver during fulminant hepatic failure (FHF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS). The results showed that the reporter gene, enhanced green fluorescent protein, was efficiently expressed in the liver of BALB/c mice. Hydrodynamic-based transfection of hHSS yielded a 70% survival rate compared with 36.7% for the control group at 24 h after D-gal/LPS treatment. In addition, hHSS expression preserved liver morphology and function. It is noteworthy that hHSS hydrodynamic-based transfer ameliorated indices of the mitochondrial permeability transition (MPT) resulting from the toxic effects of d-gal/LPS on the liver such as mitochondrial swelling, mitochondrial transmembrane potential disruption, and cytochrome c translocation. Furthermore, mitochondrial morphology and ATP levels were maintained in hHSS-administered mice. HSS-mediated protection was similar to that observed with the MPT inhibitor N-methyl-4-isoleucine-cyclosporin (NIM811), indicating a possible role for HSS in the regulation of MPT. In conclusion, a single dose of hHSS plasmid protected mice from FHF, and this hepatoprotective effect seemed to correlate with the inhibition of MPT. Topics: Adenosine Triphosphate; Animals; Blotting, Western; Cyclosporine; Cytochromes c; Cytosol; Energy Metabolism; Genetic Therapy; Green Fluorescent Proteins; Humans; Injections, Intravenous; Intercellular Signaling Peptides and Proteins; Liver; Liver Failure, Acute; Male; Membrane Potentials; Mice; Mice, Inbred BALB C; Mitochondria, Liver; Mitochondrial Swelling; Peptides; Permeability; Plasmids; Regional Blood Flow; Tail; Veins	2011

Article

Year

Administration of naked plasmid encoding hepatic stimulator substance by hydrodynamic tail vein injection protects mice from hepatic failure by suppressing the mitochondrial permeability transition.

The Journal of pharmacology and experimental therapeutics, 2011, Volume: 338, Issue:3

Acute liver failure is a devastating illness of various causes with considerable mortality. Hepatic stimulator substance (HSS) has been suggested for use as a protective agent against acute hepatic injury induced by chemical poisons because it has a variety of biological activities. However, the mechanism whereby HSS protects against hepatotoxins is poorly understood. In this study, we established a hepatic gene transfer system via hydrodynamic tail vein injection to deliver a naked plasmid containing the human HSS gene (hHSS) and analyzed HSS-mediated protection of the liver during fulminant hepatic failure (FHF) induced by D-galactosamine (D-gal) and lipopolysaccharide (LPS). The results showed that the reporter gene, enhanced green fluorescent protein, was efficiently expressed in the liver of BALB/c mice. Hydrodynamic-based transfection of hHSS yielded a 70% survival rate compared with 36.7% for the control group at 24 h after D-gal/LPS treatment. In addition, hHSS expression preserved liver morphology and function. It is noteworthy that hHSS hydrodynamic-based transfer ameliorated indices of the mitochondrial permeability transition (MPT) resulting from the toxic effects of d-gal/LPS on the liver such as mitochondrial swelling, mitochondrial transmembrane potential disruption, and cytochrome c translocation. Furthermore, mitochondrial morphology and ATP levels were maintained in hHSS-administered mice. HSS-mediated protection was similar to that observed with the MPT inhibitor N-methyl-4-isoleucine-cyclosporin (NIM811), indicating a possible role for HSS in the regulation of MPT. In conclusion, a single dose of hHSS plasmid protected mice from FHF, and this hepatoprotective effect seemed to correlate with the inhibition of MPT.

Topics: Adenosine Triphosphate; Animals; Blotting, Western; Cyclosporine; Cytochromes c; Cytosol; Energy Metabolism; Genetic Therapy; Green Fluorescent Proteins; Humans; Injections, Intravenous; Intercellular Signaling Peptides and Proteins; Liver; Liver Failure, Acute; Male; Membrane Potentials; Mice; Mice, Inbred BALB C; Mitochondria, Liver; Mitochondrial Swelling; Peptides; Permeability; Plasmids; Regional Blood Flow; Tail; Veins

2011