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ACS Applied Bio Materials Apr 2023Beta-cyclodextrin (β-CD) stabilized cerium oxide nanoparticles (β-CD@CeO NPs) were synthesized through a hydrothermal route. The electronic properties, surface...
Beta-cyclodextrin (β-CD) stabilized cerium oxide nanoparticles (β-CD@CeO NPs) were synthesized through a hydrothermal route. The electronic properties, surface functional group, surface composition, size, and morphologies of the as-synthesized β-CD@CeO NPs were characterized using UV-visible spectroscopy, FTIR analysis, high resolution X-ray photoelectron spectroscopy (HRXPS), high resolution transmission electron microscopy (HRTEM), and field emission scanning electron microscopy (FESEM). The pH-dependent variation of the ζ-potential of β-CD@CeO NPs and the catalytic activity of the NPs for the hydrolysis of paraoxon were investigated. The observed pseudo-first-order rate constant () for the hydrolysis of paraoxon is increased with increasing pH and the ζ-potential of β-CD@CeO NPs. The kinetics and mechanism of hydrolysis of paraoxon in the aqueous and cationic micellar media have been discussed.
Topics: Paraoxon; Hydrolysis; Cerium; beta-Cyclodextrins
PubMed: 36939183
DOI: 10.1021/acsabm.2c01030 -
International Journal of Molecular... Oct 2020Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood-brain barrier. Cucurbit[7]urils may be...
Antidotes against organophosphates often possess physicochemical properties that mitigate their passage across the blood-brain barrier. Cucurbit[7]urils may be successfully used as a drug delivery system for bisquaternary oximes and improve central nervous system targeting. The main aim of these studies was to elucidate the relationship between cucurbit[7]uril, oxime K027, atropine, and paraoxon to define potential risks or advantages of this delivery system in a complex in vivo system. For this reason, in silico (molecular docking combined with umbrella sampling simulation) and in vivo (UHPLC-pharmacokinetics, toxicokinetics; acetylcholinesterase reactivation and functional observatory battery) methods were used. Based on our results, cucurbit[7]urils affect multiple factors in organophosphates poisoning and its therapy by (i) scavenging paraoxon and preventing free fraction of this toxin from entering the brain, (ii) enhancing the availability of atropine in the central nervous system and by (iii) increasing oxime passage into the brain. In conclusion, using cucurbit[7]urils with oximes might positively impact the overall treatment effectiveness and the benefits can outweigh the potential risks.
Topics: Animals; Atropine; Blood-Brain Barrier; Bridged-Ring Compounds; Cholinesterase Reactivators; Computer Simulation; Imidazoles; Mice; Molecular Docking Simulation; Oximes; Paraoxon; Pyridinium Compounds
PubMed: 33114215
DOI: 10.3390/ijms21217883 -
Toxicology and Applied Pharmacology Jun 1996Kinetic parameters of parathion and paraoxon uptake were determined in isolated and perfused rabbit and guinea pig lungs. They were related to organophosphate-induced...
Kinetic parameters of parathion and paraoxon uptake were determined in isolated and perfused rabbit and guinea pig lungs. They were related to organophosphate-induced lung cholinesterase inhibition. A single pass procedure was used to perfuse the lungs with an artificial medium perfusate containing paraoxon or parathion. The paraoxon and parathion concentrations were determined in the effluents collected at chosen intervals over an 18-min period beginning at the start of perfusion. Three inflowing concentrations (1 nmol/ml, 10 nmol/ml, and 20 nmol/ml) were tested in guinea pig lungs and one (10 nmol/ml) in rabbit lungs. Cholinesterase activity was determined at time 0 and at the end of the experiment. The lungs abundantly extracted paraoxon and parathion over the perfusion period. The extraction ratio was consistently greater in guinea pig than in rabbit lungs. The uptake velocity varied biexponentially in time, suggesting the existence of two compartments. Initial uptake velocities (A, B) and slopes (alpha and beta) were calculated for both compartments. In guinea pigs, A, B and A + B increased proportionally to the supply rate of paraoxon and parathion while a and b remained constant. No significant difference was observed between parathion and paraoxon uptake kinetics. Parameter B was the only one to differ significantly between the two species (rabbits: 8.19 +/- 1.53 for parathion and 6.85 +/- 1.26 for paraoxon; guinea pigs: 12.75 +/- 0.88 for parathion and 15.02 +/- 3.84 for paraoxon). In the lungs of both species, there was a linear relation between y, the percentage of cholinesterase inhibition induced by either organophosphate, and X, the total amount of drug taken up by the lung tissue (in nmol/g/18 min). The following equations were obtained: y = 0.128 x + 0.979 (R2 = 0.89, p < 0.001 for paraoxon); y = 0.120 x - 6.57 (R2 = 0.82, p < 0.005 for parathion). No difference was observed between the two organophosphates. After treatment with the cytochrome P450 inhibitor piperonyl butoxide, the above relations ceased to apply, but this treatment did not influence the kinetics of paraoxon and parathion uptake. The IC50 value calculated for paraoxon, i.e., the paraoxon concentration required to produce 50% inhibition of lung cholinesterase activity, was similar for guinea pigs (2.22 10(-7) +/- 0.22 M) and rabbits (2.36 10(-7) +/- 0.24 M). In conclusion, the biexponential evolution of the velocity of paraoxon and parathion uptake by the lungs thus demonstrates the presence of two pools. The lower extraction ratios calculated for rabbit lungs reflect the lower initial uptake velocity of the second compartment. In the range of concentrations investigated in guinea pigs, no saturable mechanism could be demonstrated for paraoxon and parathion. Cytochrome P450-related lung metabolic activity, through which parathion is converted to paraoxon, appears as a major step in parathion-induced lung cholinesterase inhibition, although it does not appear to affect parathion toxicokinetics.
Topics: Animals; Cholinesterase Inhibitors; Female; Guinea Pigs; In Vitro Techniques; Lung; Male; Paraoxon; Parathion; Perfusion; Piperonyl Butoxide; Rabbits
PubMed: 8658521
DOI: 10.1006/taap.1996.0118 -
BMC Veterinary Research Mar 2014Paraoxonase 1 (PON1) is a widely studied enzyme based on its protective role against poisoning by organophosphate (OP) metabolites of specific OP insecticides and in... (Review)
Review
Paraoxonase 1 (PON1) is a widely studied enzyme based on its protective role against poisoning by organophosphate (OP) metabolites of specific OP insecticides and in vascular disease, as well as its use as biomarker of diseases involving oxidative stress, inflammation and liver diseases.This review provides an update about the current knowledge in the field of the analytical procedures that are used for PON1 measurements. It will be specially focused on: (a) characteristics of the different substrates used for measuring PON1, with emphasis in four aspects: toxicity, polymorphism influence, rate of hydrolysis and diagnostic performance. And (b) the technical aspects of PON1 assays, in which the reagents and reaction conditions, sources of variation, quality control systems, equipment and interferences with other esterases will be discussed.The information provided in this review can contribute to a more accurate and safe measurements of PON1 in laboratories and encourage researchers to explore the wide areas of PON1 in veterinary medicine that are still unknown.
Topics: Animals; Aryldialkylphosphatase; Humans; Insecticides; Organophosphate Poisoning; Paraoxon; Polymorphism, Genetic
PubMed: 24666514
DOI: 10.1186/1746-6148-10-74 -
Environmental Science and Pollution... Mar 2011The Chilean Altiplano ecosystem is conserved free from contaminants and pollutants because of the absence of major local human activities such as agriculture or other...
INTRODUCTION AND AIMS
The Chilean Altiplano ecosystem is conserved free from contaminants and pollutants because of the absence of major local human activities such as agriculture or other industries. We studied the effects of paraoxon on proliferation and apoptosis of testicular cells during active spermatogenesis in Dugesia gonocephala collected from a pristine river (Guacollo) in the Altiplano region nearby Visviri town, Chile.
MATERIALS AND METHODS
Adult planarians were incubated in varying concentrations of paraoxon (0.8, 0.4, 0.04, 0.004, and 0.0004 mM) for 4 h. After 3 h of incubation, bromodeoxyuridine (BrdU) was added. Effects on cell proliferation (BrdU) and apoptosis (Apaf-1) were determined by immunohistochemistry.
RESULTS
Paraoxon concentrations of 0.4 and 0.8 mM caused 100% mortality in the respective treatment groups. The lowest tested concentration (0.0004 mM) caused a significant increase on cell proliferation in the seminiferous tubules, as well as an increase in the number of apoptotic cells. All other tested concentrations significantly inhibited cell proliferation and induced apoptosis.
CONCLUSIONS
Paraoxon inhibits DNA synthesis and induces apoptosis during spermatogenesis in adult planarians from a high-altitude, pollution-free environment. This could suggest its use as a biosensor or biomarker for contamination with agro pesticides.
Topics: Animals; Apoptosis; Apoptotic Protease-Activating Factor 1; Bromodeoxyuridine; Cell Proliferation; Chile; Fresh Water; Insecticides; Paraoxon; Planarians; Spermatogenesis; Water Pollutants, Chemical
PubMed: 20865341
DOI: 10.1007/s11356-010-0385-0 -
ACS Applied Materials & Interfaces May 2017Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to target the blood-brain barrier (BBB) for drug delivery to the central nervous system (CNS)....
Solid lipid nanoparticles (SLNs) are among the most promising nanocarriers to target the blood-brain barrier (BBB) for drug delivery to the central nervous system (CNS). Encapsulation of the acetylcholinesterase reactivator, pralidoxime chloride (2-PAM), in SLNs appears to be a suitable strategy for protection against poisoning by organophosphorus agents (OPs) and postexposure treatment. 2-PAM-loaded SLNs were developed for brain targeting and delivery via intravenous (iv) administration. 2-PAM-SLNs displayed a high 2-PAM encapsulation efficiency (∼90%) and loading capacity (maximum 30.8 ± 1%). Drug-loaded particles had a mean hydrodynamic diameter close to 100 nm and high negative zeta potential (-54 to -15 mV). These properties contribute to improve long-term stability of 2-PAM-SLNs when stored both at room temperature (22 °C) and at 4 °C, as well as to longer circulation time in the bloodstream compared to free 2-PAM. Paraoxon-poisoned rats (2 × LD) were treated with 2-PAM-loaded SLNs at a dose of 2-PAM of 5 mg/kg. 2-PAM-SLNs reactivated 15% of brain AChE activity. Our results confirm the potential use of SLNs loaded with positively charged oximes as a medical countermeasure both for protection against OPs poisoning and for postexposure treatment.
Topics: Animals; Brain; Cholinesterase Reactivators; Lipids; Nanoparticles; Paraoxon; Pralidoxime Compounds; Rats
PubMed: 28504886
DOI: 10.1021/acsami.7b04163 -
Journal of the American Chemical Society Mar 2021Melanin is a ubiquitous natural pigment found in a diverse array of organisms. Allomelanin is a class of nitrogen-free melanin often found in fungi. Herein, we find...
Melanin is a ubiquitous natural pigment found in a diverse array of organisms. Allomelanin is a class of nitrogen-free melanin often found in fungi. Herein, we find artificial allomelanin analogues exhibit high intrinsic microporosity and describe an approach for further increasing and tuning that porosity. Notably, the synthetic method involves an oxidative polymerization of 1,8-DHN in water, negating the need for multiple complex templating steps and avoiding expensive or complex chemical precursors. The well-defined morphologies of these nanomaterials were elucidated by a combination of electron microscopy and scattering methods, yielding to high-resolution 3D reconstruction based on small-angle X-ray scattering (SAXS) results. Synthetic allomelanin nanoparticles exhibit high BET areas, up to 860 m/g, and are capable of ammonia capture up to 17.0 mmol/g at 1 bar. In addition, these nanomaterials can adsorb nerve agent simulants in solution and as a coating on fabrics with high breathability where they prevent breakthrough. We also confirmed that naturally derived fungal melanin can adsorb nerve gas simulants in solution efficiently despite lower porosity than synthetic analogues. Our approach inspires further analysis of yet to be discovered biological materials of this class where melanins with intrinsic microporosity may be linked to evolutionary advantages in relevant organisms and may in turn inspire the design of new high surface area materials.
Topics: Adsorption; Biopolymers; Fungi; Melanins; Nanoparticles; Naphthols; Paraoxon; Porosity; Scattering, Small Angle; X-Ray Diffraction
PubMed: 33673734
DOI: 10.1021/jacs.1c00748 -
Inorganic Chemistry May 2000We report the first case of an organometallic complex that effectively hydrolyzes the organophosphate pesticides parathion and paraoxon. The complex is the water-soluble...
We report the first case of an organometallic complex that effectively hydrolyzes the organophosphate pesticides parathion and paraoxon. The complex is the water-soluble compound bis(eta 5-cyclopentadienyl)molybdenum(IV) dichloride (1), which hydrolyzes parathion to produce ethanol and deethyl parathion in a biphasic reaction in D2O. Rate accelerations were 130 and 10(5) at pH 7 and 3, respectively. Paraoxon is readily hydrolyzed by 1 to yield p-nitrophenol and diethyl phosphate with rate accelerations of 2300 and 27 at pH 7 and 3, respectively. Kinetic data for paraoxon hydrolysis by 1 are consistent with a process that involves intermolecular (delta S++ = -49 +/- 10 eu) hydroxide attack on the phosphate triester in which the aquated 1 serves as a coordinated Lewis acid that activates the organophosphate. Interestingly parathion hydrolysis by 1 occurs via nucleophilic attack at the alpha-carbon of the phosphorothioate pesticide that involves C-O bond cleavage. These parathion results represent one of the few cases of this type of unusual hydrolytic chemistry and the first case of an organometallic complex that accelerates organophosphate pesticide hydrolysis.
Topics: Catalysis; Hydrogen-Ion Concentration; Hydrolysis; Insecticides; Kinetics; Magnetic Resonance Spectroscopy; Molecular Structure; Organometallic Compounds; Paraoxon; Parathion; Temperature
PubMed: 12526519
DOI: 10.1021/ic991134k -
Magnetic Resonance in Chemistry : MRC Mar 2014Cyclodextrins are torus-shaped polymers of glucose that can bind organophosphorous compounds such as nerve agents and pesticides. We demonstrate here that cyclodextrin...
Cyclodextrins are torus-shaped polymers of glucose that can bind organophosphorous compounds such as nerve agents and pesticides. We demonstrate here that cyclodextrin can bind up to two paraoxon molecules with a K(av) of 6775 M(-1). Molecular modeling shows that the paraoxon appears to bind in polar opposite orientation and have an average binding energy of -89 Kcals/mol. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
Topics: Cyclodextrins; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Paraoxon; Reference Standards
PubMed: 24357355
DOI: 10.1002/mrc.4036 -
Clinical Biochemistry Oct 2009To set-up a method for a direct evaluation in human serum of paraoxonase enzymatic activities, establishing a possible correlation with Q192R genotype polymorphism.
OBJECTIVES
To set-up a method for a direct evaluation in human serum of paraoxonase enzymatic activities, establishing a possible correlation with Q192R genotype polymorphism.
DESIGN AND METHODS
101 different human serum samples were genotyped for paraoxonase Q192R polymorphism by PCR restriction analysis, and evaluated spectrophotometrically with regard to paraoxon and 2-coumaranone hydrolytic activities. Both activities of paraoxonase were assayed, quantified through normalization by arylesterase activity, and compared with the data concerning Q/R genetic polymorphism.
RESULTS
The mean normalized paraoxonase activity was found to be significantly higher in RR than in QQ human sera (3.99+/-0.6 versus 1.32+/-0.44; P<0.0001); instead, the 2-coumaranone hydrolysis showed an opposite trend (0.10+/-0.02 versus 0.23+/-0.04, in RR and QQ sera respectively; P<0.0001).
CONCLUSIONS
These methods were successfully applied to the whole serum, suggesting a possible use of this approach for a clinically relevant phenotypic characterization.
Topics: Adult; Aryldialkylphosphatase; Benzofurans; Cholinesterase Inhibitors; Genotype; Humans; Middle Aged; Paraoxon; Polymorphism, Genetic; Substrate Specificity
PubMed: 19615988
DOI: 10.1016/j.clinbiochem.2009.07.006