Effects of paraoxon on neuronal and lymphocytic cholinergic systems.

The cholinergic system in lymphocytes is hypothesized to be a key target for neurotoxic organophosphates (OPs). The present study determined the comparative effects of paraoxon, the active metabolite of OP-parathion, which is detected in the human neuroblastoma line, SH-SY5Y, and leukemic T-lymphocytes, MOLT-3, in vitro. Paraoxon induced cytotoxic effects in a dose- and time-dependent manner in both cells. Further, the paraoxon-induced modulatory effects were comparable despite different cell types, including over-expression of N-terminus acetylcholinesterase (N-AChE) protein, a marker of apoptosis, down-regulations of mRNA encoding M1, M2, and M3 muscarinic acetylcholine receptors (mAChRs), and induction in expression of c-Fos gene, an indication of certain mAChR subtype(s) activation. Furthermore, the non-selective cholinergic antagonist atropine partially attenuated the paraoxon-induced N-AChE and c-Fos activations in both types of cells. These results provide initial and additional information that OPs may similarly induce neuro- and immuno-toxic effects through mAChRs activation, and they underline the potential of using lymphocytes for assessing OPs-induced neurotoxicity.
AuthorsTanvisith Charoenying, Tawit Suriyo, Apinya Thiantanawat, Sansanee C Chaiyaroj, Preeda Parkpian, Jutamaad Satayavivad
JournalEnvironmental toxicology and pharmacology (Environ Toxicol Pharmacol) Vol. 31 Issue 1 Pg. 119-28 (Jan 2011) ISSN: 1872-7077 [Electronic] Netherlands
PMID21787676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010. Published by Elsevier B.V.
Chemical References
  • Cholinesterase Inhibitors
  • Coloring Agents
  • Indicators and Reagents
  • Muscarinic Agonists
  • Receptor, Muscarinic M1
  • Receptor, Muscarinic M2
  • Receptor, Muscarinic M3
  • Tetrazolium Salts
  • Thiazoles
  • thiazolyl blue
  • Acetylcholinesterase
  • Paraoxon
  • Acetylcholinesterase (metabolism)
  • Blotting, Western
  • Cell Line
  • Cell Survival (drug effects)
  • Cholinesterase Inhibitors (toxicity)
  • Coloring Agents
  • Genes, fos (drug effects)
  • Humans
  • Indicators and Reagents
  • Lymphocytes (drug effects)
  • Muscarinic Agonists (toxicity)
  • Neurons (drug effects)
  • Paraoxon (toxicity)
  • Parasympathetic Nervous System (cytology, drug effects)
  • Real-Time Polymerase Chain Reaction
  • Receptor, Muscarinic M1 (drug effects)
  • Receptor, Muscarinic M2 (drug effects)
  • Receptor, Muscarinic M3 (drug effects)
  • Tetrazolium Salts
  • Thiazoles

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