Organophosphorus neuropathy target esterase inhibitors selectively block outgrowth of neurite-like and cell processes in cultured cells.

Abstract

This study compares two direct-acting neuropathy target esterase (NTE) inhibitors (mipafox and 2-octyl-4H-1,3,2-benzodioxophosphorin 2-oxide (OBDPO)), a metabolic precursor to an NTE inhibitor (tri-o-cresyl phosphate or TOCP) and a potent acetylcholinesterase inhibitor (chlorpyrifos oxon or CPO) for their effects on outgrowth of neurite-like and cell processes and on viability in differentiated cultured cells (rat adrenal pheochromocytoma (PC-12) and brain glial tumor (C6)). The direct-acting NTE inhibitors block process outgrowth by 50% or more at 50-100 microM for OBDPO and 100-200 microM for mipafox, well below their cytotoxic levels (EC50 values, 445-474 microM for OBDPO and 1021-1613 microM for mipafox). In contrast, the effects on process development for TOCP and CPO parallel their cytotoxicity. These findings suggest that inhibition of neurite-like and cell process outgrowth by OBDPO and mipafox may be associated with NTE inhibition.

• Authors: W Li, J E Casida
• Journal: Toxicology letters (Toxicol Lett) Vol. 98 Issue 3 Pg. 139-46 (Sep 15 1998) ISSN: 0378-4274 [Print] Netherlands
• PMID: 9788582 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 2-octyl-4H-1,3,2-benzodioxaphosphorin-2-oxide
• Cholinesterase Inhibitors
• Enzyme Inhibitors
• Organophosphorus Compounds
• Tritolyl Phosphates
• Isoflurophate
• mipafox
• O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate
• Carboxylic Ester Hydrolases
• neurotoxic esterase
• Acetylcholinesterase
• Chlorpyrifos
• tri-o-cresyl phosphate

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Carboxylic Ester Hydrolases (antagonists & inhibitors, metabolism)
• Cell Differentiation
• Cell Survival (drug effects)
• Chlorpyrifos (analogs & derivatives, pharmacology)
• Cholinesterase Inhibitors (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Isoflurophate (analogs & derivatives, pharmacology)
• Neurites (drug effects, enzymology)
• Organophosphorus Compounds (pharmacology)
• Sensitivity and Specificity
• Tritolyl Phosphates (pharmacology)
• Tumor Cells, Cultured (drug effects, enzymology)