Fullerene antioxidants decrease organophosphate-induced acetylcholinesterase inhibition in vitro

Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.
Toxicology in Vitro (Impact Factor: 3.21). 09/2010; 25(1):301-7. DOI: 10.1016/j.tiv.2010.09.010
Source: PubMed

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: This study focuses on the utility of strategically functionalized fullerene nanomaterials as a potential alternative therapy for inhaled corticosteroids, specifically in regards to mast cell mediated allergic inflammation. Myo-Inositol modified 70-carbon fullerenes (C70-I) are taken up by mast cells and result in down-regulation of MAPK via DUSP1 induction, similar to inhaled corticosteroids, resulting in significant inhibitions of inflammatory mediator release (degranulation and GM-CSF cytokine release).
    Nanomedicine: nanotechnology, biology, and medicine 08/2014; 10(6). DOI:10.1016/j.nano.2014.02.006 · 5.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to investigate the effects of water soluble fullerene (fullerenol) nanoparticles on the in vitro genotoxicity induced by the insecticide acetamiprid. Healthy human lung cells (IMR-90) were treated with fullerenol C60(OH)n (n: 18-22) alone and in combination with acetamiprid for 24h. The micronucleus test, comet assay and γ-H2AX foci formation assays were used as genotoxicity endpoints. Cytotoxicity was evaluated using the clonogenic assay. The maximum tested concentration of fullerenol (1.600μg/ml) induced 77% survival where as the lowest concentration (25μg/ml) was not cytotoxic where as acetamiprid was cytotoxic. Fullerenol did not induce genotoxicity at tested concentrations (50-1600μg/L). On the other hand, acetamiprid (>50μM) significantly induced formation of micronuclei, and double and single stranded DNA breaks in IMR-90 cells. For simultaneous exposure studies, two non-cytotoxic concentrations (50 and 200μg/ml) of fullerenol and three cytotoxic concentrations of acetamiprid (100, 200 and 400μM) were selected. As a result, we observed that co-exposure with fullerenol significantly reduced the cytotoxicity and genotoxicity of acetamiprid in IMR-90 cells. Our results indicated the protective effect of water soluble fullerene particles on herbicide induced genotoxicity.
    Pesticide Biochemistry and Physiology 09/2014; 114. DOI:10.1016/j.pestbp.2014.07.008 · 2.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The effect of polyhydroxylated fullerene (fullerenol), C60(OH)36, on human peripheral blood mononuclear cells (PBMCs) exposed to X-rays was studied. PBMCs untreated and treated for 1 h with C60(OH)36 at the concentrations 75 and 150 mg/l were exposed to high doses of ionizing radiation (10, 30 and 50 Gy). After 24 and 48 h of post-irradiation incubation the viability and granularity of lymphocytes were determined applying the flow cytometry (FC) method. Moreover, after 24 h of incubation the membrane fluidity was investigated by measuring the fluorescence anisotropy of a 1,6-diphenyl-1,3,5-hexatriene (DPH) probe. Additionally, DNA damage of PBMCs after exposure to X-rays at the doses 0, 5, 10 and 15 Gy in the absence and presence of fullerenol (75 mg/l) was determined using the comet assay under alkaline conditions. Results show that the effects of fullerenol C60(OH)36 on X-irradiated human PBMCs are very small or inexistent. It was suggested that this action of C60(OH)36 may be related to its interactions with the surface of plasma membrane but not inside PBMCs.
    Radiation Physics and Chemistry 04/2014; 97:325-331. DOI:10.1016/j.radphyschem.2013.12.022 · 1.19 Impact Factor