These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Gene therapy to prevent organophosphate intoxication.
    Author: Cowan J, Sinton CM, Varley AW, Wians FH, Haley RW, Munford RS.
    Journal: Toxicol Appl Pharmacol; 2001 May 15; 173(1):1-6. PubMed ID: 11350209.
    Abstract:
    The specific hydrolytic activity of PON1 paraoxonase/arylesterase enzymes in liver and blood provides a natural barrier against the entry of organophosphate toxins into the central and peripheral nervous systems. Inherited differences in PON1 enzyme concentrations may determine levels of susceptibility to organophosphate injury in humans. To test whether boosting serum levels of PON1 enzymes by gene therapy might provide increased protection, we compared the degree of inactivation of whole brain acetylcholinesterase of mice exposed to chlorpyrifos 4 days after intravenous injection of recombinant adenoviruses containing PON1-LQ or PON1-LR genes or no PON1 gene. Both recombinant viruses containing PON1 genes boosted serum arylesterase concentrations by approximately 60% and significantly prevented the inactivation of brain acetylcholinesterase. Some mice were completely protected. These findings indicate that boosting serum levels of PON1 enzymes by a gene delivery vector raises the threshold for organophosphate toxicity by hydrolytic destruction before the chemical can enter the brain.
    [Abstract] [Full Text] [Related] [New Search]