Influence of method of systemic administration of adenovirus on virus-mediated toxicity: focus on mortality, virus distribution, and drug metabolism.

Journal of Pharmacological and Toxicological Methods
Michael P BoquetMaria A Croyle

Abstract

Doses of 2 x 10(12) virus particles/kilogram (vp/kg) and higher of recombinant human adenovirus serotype 5 (HAdV-5) given via the tail vein induce significant toxicity and mortality in the rat. This was not observed when doses of 5.7 x 10(12) vp/kg were given through a surgically implanted jugular catheter. Here we assess how the manner by which HAdV-5 is introduced into the systemic circulation affects biodistribution, transgene expression, toxicity and mortality 0.25, 1, and 4 days after treatment in the rat. Animals were given 5.7 x 10(12) vp/kg of HAdV-5 expressing beta-galactosidase or saline through a jugular catheter or by direct tail vein injection. All animals survived after jugular vein dosing. Tail vein injection of HAdV-5 increased the mortality rate to 42% (p< or =0.01). All deaths occurred within 4 h. Animals dosed through the jugular vein had significantly higher levels of transgene expression in the liver and spleen and significantly more viral genomes in these tissues and kidney and lung within the first 24 h of viral infection compared to those dosed by tail vein injection (p< or =0.01). There was no significant difference between the groups thereafter. Samples from animals that died contained even higher leve...Continue Reading

References

Aug 1, 1977·Journal of Pharmaceutical Sciences·L I Harrison, M Gibaldi
Jan 1, 1990·Trends in Biochemical Sciences·C N Pace
Nov 1, 1986·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·C N SmithR D Irons
Apr 1, 1973·Virology·F L Graham, A J van der Eb
May 1, 1983·Journal of Pharmaceutical Sciences·D M Cocchetto, T D Bjornsson
Feb 1, 1993·Archives of Neurology·C A Thornton, M Ballow
May 1, 1997·Journal of Pharmaceutical Sciences·J BrangeE Rasmussen
Jan 17, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Andrew A ShawRaymond E Galinsky
Jan 29, 2002·Toxicological Sciences : an Official Journal of the Society of Toxicology·Richard E MorrisseyJames S MacDonald
Sep 28, 2002·Molecular Therapy : the Journal of the American Society of Gene Therapy·Harvey Ben-GaryRonald G Crystal
Nov 15, 2002·Brain Research. Brain Research Protocols·K V ThrivikramanPaul M Plotsky
Mar 1, 1965·Canadian Journal of Physiology and Pharmacology·R P RANDT ING
Mar 18, 2004·Journal of Endotoxin Research·Zhonghua Li, Clark M Blatteis
Jun 15, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jeffrey S SmithAndrew P Byrnes
Oct 22, 2004·The Journal of Pharmacology and Experimental Therapeutics·Shellie M CallahanMaria A Croyle
Aug 6, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alla Y RudayaAndrej A Romanovsky
Mar 2, 2006·The Journal of Gene Medicine·Shellie M CallahanMaria A Croyle
Mar 27, 2007·Cancer Letters·Markus J V Vähä-KoskelaAri E Hinkkanen
Apr 25, 2007·International Journal of Medical Microbiology : IJMM·Thomas GutsmannKlaus Brandenburg
May 17, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Andrew H BakerDmitry M Shayakhmetov
Jun 23, 2007·Current Gene Therapy·Samuel K Campos, Michael A Barry
Jul 10, 2007·Journal of Pharmacological and Toxicological Methods·Yu-hua HuiNita Patel
Jul 21, 2007·International Journal of Pharmaceutics·Haruna SakuraiHiroyuki Mizuguchi
Oct 4, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Florian Kreppel, Stefan Kochanek
Nov 30, 2007·Gene Therapy·A Zaldumbide, R C Hoeben
Jan 26, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Edward T MorganChristopher J Sinal
Feb 23, 2008·Toxicology·Josef OzerShelli Schomaker
May 2, 2008·Human Gene Therapy·Jeffrey S SmithAndrew P Byrnes
May 13, 2008·Methods in Molecular Biology·Hongju Wu, David T Curiel
Jun 17, 2008·Nature Reviews. Microbiology·Roberto CattaneoMichael A Barry

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.