Fullerene antioxidants decrease organophosphate-induced acetylcholinesterase inhibition in vitro.

Abstract

Although organophosphate (OP)-induced acetylcholinesterase (AChE) inhibition is the critical mechanism causing toxicities that follow exposure, other biochemical events, including oxidative stress, have been reported to contribute to OP toxicity. Fullerenes are carbon spheres with antioxidant activity. Thus, we hypothesized that fullerenes could counteract the effects of OP compounds and tested this hypothesis using two in vitro test systems, hen brain and human neuroblastoma SH-SY5Y cells. Cells were incubated with eight different derivatized fullerene compounds before challenge with paraoxon (0=control, 5×10(-8), 10(-7), 2×10(-7) or 5×10(-7) M) or diisopropylphosphorofluoridate (DFP, 0=control, 5×10(-6), 10(-5), 2×10(-5), and 5×10(-5) M) and measurement of AChE activities. Activities of brain and SH-SY5Y AChE with OP compounds alone ranged from 55-83% lower than non-treated controls after paraoxon and from 60-92% lower than non-treated controls after DFP. Most incubations containing 1 and 10 μM fullerene derivatives brought AChE activity closer to untreated controls, with improvements in AChE activity often >20%. Using dissipation of superoxide anion radicals as an indicator (xanthine oxidation as a positive control), all fullerene derivatives demonstrated significant antioxidant capability in neuroblastoma cells at 1 μM concentrations. No fullerene derivative at 1 μM significantly affected neuroblastoma cell viability, when determined using either Alamar Blue dye retention or a luminescent assay for ATP production. These studies suggest that derivatized fullerene nanomaterials have potential capability to ameliorate OP-induced AChE inhibition resulting in toxicities.

• Authors: Marion Ehrich, Roger Van Tassell, Yunbo Li, Zhiguo Zhou, Chris L Kepley
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 25 Issue 1 Pg. 301-7 (Feb 2011) ISSN: 1879-3177 [Electronic] England
• PMID: 20888407 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Cholinesterase Inhibitors
• Cholinesterase Reactivators
• Fullerenes
• Organophosphates
• Superoxides
• Isoflurophate
• Acetylcholinesterase
• Paraoxon

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Antioxidants (chemistry, pharmacology, toxicity)
• Brain (cytology, enzymology, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cells, Cultured
• Chickens
• Cholinesterase Inhibitors (toxicity)
• Cholinesterase Reactivators (chemistry, pharmacology, toxicity)
• Embryo, Mammalian
• Fullerenes (chemistry, pharmacology, toxicity)
• Humans
• Isoflurophate (antagonists & inhibitors, toxicity)
• Mice
• Neuroblastoma
• Neurons (enzymology, metabolism)
• Organophosphates (antagonists & inhibitors, toxicity)
• Paraoxon (antagonists & inhibitors, toxicity)
• Superoxides (metabolism)