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Biochemistry. Biokhimiia Feb 2023Exposure to paraoxon (POX) and leptin (LP) could cause an imbalance between oxidants and antioxidants in an organism, which can be prevented by introduction of exogenous...
Exposure to paraoxon (POX) and leptin (LP) could cause an imbalance between oxidants and antioxidants in an organism, which can be prevented by introduction of exogenous antioxidants such as N-acetylcysteine (NAC). The aim of this study was to evaluate synergic or additive effects of administration of exogenous LP plus POX on the antioxidant status, as well as the prophylactic and therapeutic roles of NAC in various rat tissues. Fifty-four male Wistar rats were divided into nine groups treated with different compounds: Control (no treatment), POX (0.7 mg/kg), NAC (160 mg/kg), LP (1 mg/kg), POX+LP, NAC-POX, POX-NAC, NAC-POX+LP, and POX+LP-NAC. In the last five groups, only the order of administered compounds differed. After 24 h, plasma and tissues were sampled and examined. The results showed that administration of POX plus LP significantly increased biochemical indices in plasma and antioxidant enzymes activities and decreased glutathione content in the liver, erythrocytes, brain, kidney, and heart. In addition, cholinesterase and paraoxonase 1 activities in the POX+LP-treated group were decreased and malondialdehyde level was increased in the liver, erythrocytes, and brain. However, administration of NAC rectified induced changes although not to the same extent. Our study suggests that POX or LP administration engage the oxidative stress system per se; however, their combination did not produce significantly greater effects. Moreover, both prophylactic and therapeutic treatments of rats with NAC supported the antioxidant defense against oxidative damage in tissues, most probably through both its free radical scavenging ability and maintaining intracellular GSH levels. It can therefore be suggested that NAC has particularly protective effects against POX or/and LP toxicity.
Topics: Rats; Male; Animals; Antioxidants; Acetylcysteine; Paraoxon; Rats, Wistar; Leptin; Oxidative Stress
PubMed: 37072331
DOI: 10.1134/S0006297923020013 -
Toxicology Letters Oct 1981Acetylcholinesterase (AChE) activity of cultured chick embryonic pectoral muscle was significantly increased above control activity during recovery from brief treatments...
Acetylcholinesterase (AChE) activity of cultured chick embryonic pectoral muscle was significantly increased above control activity during recovery from brief treatments with paraoxon (O, O-diethyl-p-nitrophenyl phosphate), the anticholinesterase metabolite of parathion. Paraoxon also increased the rate of degradation of the enzyme, suggesting the higher AChE activity of paraoxon-treated cells was due to a stimulation of enzyme synthesis.
Topics: Acetylcholinesterase; Animals; Chick Embryo; Cycloheximide; Kinetics; Muscles; Organ Culture Techniques; Paraoxon
PubMed: 7302984
DOI: 10.1016/0378-4274(81)90029-1 -
Ecotoxicology and Environmental Safety Jul 2022Exogenous pollution of Chinese medicinal materials by pesticide residues and heavy metal ions has attracted great attention. Relying on the rapid development of...
Exogenous pollution of Chinese medicinal materials by pesticide residues and heavy metal ions has attracted great attention. Relying on the rapid development of nanotechnology and multidisciplinary fields, fluorescent techniques have been widely applied in contaminant detection and pollution monitoring due to their advantages of simple preparation, low cost, high throughput and others. Most importantly, synchronous detection of multi-targets has always been pursued as one of the major goals in the design of fluorescent probes. Herein, we firstly develop a simultaneous sensing method for methyl-paraoxon (MP) and Nickel ion (Ni, Ⅱ) by using carbon based fluorescent nanocomposite with ratiometric signal readout and nanozyme. Notably, the designed system showed excellent effectiveness even when the two pollutants co-exist. Under the optimum conditions, this method provides low limits of detection of 1.25 µM for methyl-paraoxon and 0.01 µM for Ni (Ⅱ). To further verify the reliability, recovery studies of these two analytes were performed on ginseng radix et rhizoma, nelumbinis semen, and water samples. In addition, smartphone-based visual analysis has been introduced to expand its applicability in point of care detection. This work not only expands the application of the dual-mode approach to pollutant detection, but also provides insights into the analysis of multiple pollutants in a single assay.
Topics: Environmental Pollutants; Fluorescent Dyes; Limit of Detection; Paraoxon; Pesticide Residues; Reproducibility of Results
PubMed: 35623151
DOI: 10.1016/j.ecoenv.2022.113668 -
Journal of Colloid and Interface Science Nov 2018Organophosphate compounds that are used as pesticides affect the nervous system by binding irreversibly to the active site of the enzyme acetylcholine esterase (AChE)...
Organophosphate compounds that are used as pesticides affect the nervous system by binding irreversibly to the active site of the enzyme acetylcholine esterase (AChE) and disrupting neuro-signaling nerve cells. In this study we characterized adsorption of paraoxon to a set of designed peptides that present different arrangements of the three amino acids of the AChE catalytic site: histidine, glutamic-acid and serine. The peptides set included two β-strands with no net charge and three β-hairpins that differ in their net charge. Circular dichroism, Thioflavin T assays and TEM images provided only qualitative insights on paraoxon binding to the different peptides. Paraoxon binding to the different peptides was measured with dialysis membrane tubes filled with the peptide solutions and suspended in a reservoir of paraoxon solution. Among all the tested peptides, the single strand peptide, denoted ssESH exhibited at 100 μM in random conformation prefibrillar state, the maximum paraoxon adsorption, with a binding mol ratio of one paraoxon per two peptides and an estimated equilibrium binding constant 5 ∗ 10 M. The three β-hairpin peptides demonstrated that a net negative charge is unfavorable for paraoxon adsorption. Surface enhanced Raman spectroscopy measurements with ssESH enabled the detection of nanomolar adsorbed concentrations of paraoxon.
Topics: Acetylcholinesterase; Adsorption; Catalytic Domain; Cholinesterase Inhibitors; Humans; Insecticides; Paraoxon; Peptides; Protein Conformation, beta-Strand; Spectrum Analysis, Raman
PubMed: 29982025
DOI: 10.1016/j.jcis.2018.06.065 -
Environmental Science. Processes &... Dec 2022Parathion, a once commonly used pesticide known for its potential toxicity, can follow several degradation mechanisms in the environment. Given the species stability and...
Parathion, a once commonly used pesticide known for its potential toxicity, can follow several degradation mechanisms in the environment. Given the species stability and persistence, parathion can be washed into waterways from rain, and therefore an atomistic perspective of the hydrolysis of parathion, and its byproduct paraoxon, is required in order to understand its fate in the environment. Experimental studies have determined that pH plays an important role in the calculated hydrolysis rate constants of parathion degradation. In this work, the degradation of parathion into either paraoxon or 4-nitrophenol, and the degradation of paraoxon to 4-nitrophenol are explored through density functional theory using the M06-2X functional. How the level of basicity affects the reaction mechanism is explored through two different hydroxide/water environments. Our calculations support the anticipated mechanisms determined by previous experimental work that the formation of 4-nitrophenol is the predominant pathway in hydrolysis of parathion.
Topics: Parathion; Paraoxon; Hydrolysis; Density Functional Theory
PubMed: 36129094
DOI: 10.1039/d2em00296e -
Journal of Hazardous Materials Mar 2022Fuller's earth (FE) is a phyllosilicate used as a powder for household or skin decontamination due to its adsorbent properties. Recent studies have shown that water...
Fuller's earth (FE) is a phyllosilicate used as a powder for household or skin decontamination due to its adsorbent properties. Recent studies have shown that water suspensions exhibit similar adsorbent capacities. FE is heterogeneous due to its composition of elementary clay aggregates and heavy metal particles. Here, FE toxicity was assessed in vitro on skin cells and in vivo on Danio rerio embryos. Among the suspensions tested (5%, 9.1% and 15% w/w), only the highest one shows weak toxicity. Suspensions were tested for ex vivo dermal decontamination into pig ear skin and human abdominal skin using diffusion cells and paraoxon as organophosphorus contaminant. After 24 h of diffusion, no difference was observed in the paraoxon concentration in the receptor compartment whether the decontamination was carried out with FE in powder or in suspension form. In presence of FE suspensions, we observed the disappearance of paraoxon from the stratum corneum, the reservoir compartment, independently of the suspensions' concentration. We suggest that water potentiates the absorbing capacities of FE powder by intercalating between clay lamellas leading to the appearance of new adsorption zones and swelling. These data support the use of FE aqueous suspensions as a safe tool for organophosphorus skin decontamination.
Topics: Adsorption; Aluminum Compounds; Animals; Decontamination; Magnesium Compounds; Paraoxon; Silicates; Skin; Suspensions; Swine; Water
PubMed: 34896712
DOI: 10.1016/j.jhazmat.2021.127714 -
Chemical Research in Toxicology Nov 2010SH-SY5Y neuroblastoma cells were examined to determine changes in protein expression following exposure to the organophosphate paraoxon (O,O-diethyl-p-nitrophenoxy...
SH-SY5Y neuroblastoma cells were examined to determine changes in protein expression following exposure to the organophosphate paraoxon (O,O-diethyl-p-nitrophenoxy phosphate). Exposure of SH-SY5Y cells to paraoxon (20 μM) for 48 h showed no significant change in cell viability as established using an MTT assay. Protein expression changes from the paraoxon-treated SH-SY5Y cells were determined using a comparative, subproteome approach by fractionation into cytosolic, membrane, nuclear, and cytoskeletal fractions. The fractionated proteins were separated by 2D-PAGE, identified by MALDI-TOF mass spectrometry, and expression changes determined by densitometry. Over 400 proteins were separated from the four fractions, and 16 proteins were identified with altered expression ≥1.3-fold including heat shock protein 90 (-1.3-fold), heterogeneous nuclear ribonucleoprotein C (+2.8-fold), and H(+) transporting ATP synthase beta chain (-3.1-fold). Western blot analysis conducted on total protein isolates confirmed the expression changes in these three proteins.
Topics: Blotting, Western; Cell Line, Tumor; Electrophoresis, Gel, Two-Dimensional; HSP90 Heat-Shock Proteins; Heterogeneous-Nuclear Ribonucleoprotein Group C; Humans; Insecticides; Paraoxon; Proteome; Proton-Translocating ATPases; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 20931991
DOI: 10.1021/tx100192f -
Applied Microbiology and Biotechnology Oct 2007Organophosphate (OP) poisoning can occur through unintentional exposure to OP pesticides, or by the deliberate release of OP nerve agents. Consequently, there is...
Organophosphate (OP) poisoning can occur through unintentional exposure to OP pesticides, or by the deliberate release of OP nerve agents. Consequently, there is considerable interest in the development of systems that can detect and/or biodegrade these agents. The aim of this study was to generate a prototype fluorescent reporter yeast biosensor that could detect and biodegrade the model OP pesticide, paraoxon, and subsequently detect paraoxon hydrolysis. Saccharomyces cerevisiae was engineered to hydrolyze paraoxon through the heterologous expression of the Flavobacterium species opd (organophosphate degrading) gene. Global transcription profiling was subsequently used to identify yeast genes, which were induced in the presence of paraoxon, and genes, which were associated with paraoxon hydrolysis. Paraoxon-inducible genes and genes associated with paraoxon hydrolysis were identified. Candidate paraoxon-inducible promoters were cloned and fused to the yeast-enhanced green fluorescent protein (yEGFP), and candidate promoters associated with paraoxon hydrolysis were fused to the red fluorescent protein (yDsRed). The ability of the yeast biosensor to detect paraoxon and paraoxon hydrolysis was demonstrated by the specific induction of the fluorescent reporter (yEGFP and yDsRed, respectively). Biosensors responded to paraoxon in a dose- and time-dependent manner, and detection was rapid (15 to 30 min). yDsRed induction occurred only in the recombinant opd(+) strains suggesting that yDsRed induction was strictly associated with paraoxon hydrolysis. Together, these results indicate that the yeast biocatalyst-biosensor can detect and degrade paraoxon and potentially also monitor the decontamination process.
Topics: Aryldialkylphosphatase; Biodegradation, Environmental; Biosensing Techniques; Cholinesterase Inhibitors; Gene Expression Profiling; Gene Expression Regulation, Fungal; Genetic Engineering; Organophosphates; Paraoxon; Promoter Regions, Genetic; Protein Array Analysis; Saccharomyces cerevisiae; Water Pollutants, Chemical
PubMed: 17665192
DOI: 10.1007/s00253-007-1107-5 -
Toxicology and Applied Pharmacology Apr 1999This investigation effort is focused on increasing organophosphate (OP) degradation by phosphotriesterase to antagonize OP intoxication. For these studies, sterically...
This investigation effort is focused on increasing organophosphate (OP) degradation by phosphotriesterase to antagonize OP intoxication. For these studies, sterically stabilized liposomes encapsulating recombinant phosphotriesterase were employed. This enzyme was obtained from Flavobacterium sp. and was expressed in Escherichia coli. It has a broad substrate specificity, which includes parathion, paraoxon, soman, sarin, diisopropylfluorophosphate, and other organophosphorous compounds. Paraoxon is rapidly hydrolyzed by phosphotriesterase to the less toxic 4-nitrophenol and diethylphosphate. This enzyme was isolated and purified over 1600-fold and subsequently encapsulated within sterically stabilized liposomes (SL). The properties of this encapsulated phosphotriesterase were investigated. When these liposomes containing phosphotriesterase were incubated with paraoxon, it readily degraded the paraoxon. Hydrolysis of paraoxon did not occur when these sterically stabilized liposomes contained no phosphotriesterase. These sterically stabilized liposomes (SL) containing phosphotriesterases (SL)* were employed as a carrier model to antagonize the toxic effects of paraoxon by hydrolyzing it to the less toxic 4-nitrophenol and diethylphosphate. This enzyme-SL complex (SL)* was administered intravenously to mice either alone or in combination with pralidoxime (2-PAM) and/or atropine intraperitoneally. These results indicate that this carrier model system provides a striking enhanced protective effects against the lethal effects of paraoxon. Moreover when these carrier liposomes were administered with 2-PAM and/or atropine, a dramatic enhanced protection was observed.
Topics: Animals; Aryldialkylphosphatase; Drug Carriers; Esterases; Insecticides; Isoelectric Point; Liposomes; Male; Mice; Mice, Inbred BALB C; Paraoxon; Pralidoxime Compounds; Recombinant Proteins
PubMed: 10101099
DOI: 10.1006/taap.1998.8620 -
Chemistry, An Asian Journal Jul 2022The enzymatic degradation of pesticides paraoxon (PON) and parathion (PIN) by phosphotriesterase (PTE) has been investigated by QM/MM calculations and MD simulations. In...
The enzymatic degradation of pesticides paraoxon (PON) and parathion (PIN) by phosphotriesterase (PTE) has been investigated by QM/MM calculations and MD simulations. In the PTE-PON complex, Zn and Zn in the active site are five- and six-coordinated, respectively, while both zinc ions are six coordinated with the Zn -bound water molecule (WT1) for the PTE-PIN system. The hydrolytic reactions for PON and PIN are respectively driven by the nucleophilic attack of the bridging-OH and the Zn -bound water molecule on the phosphorus center of substrate, and the two-step hydrolytic process is predicted to be the rate-limiting step with the energy spans of 13.8 and 14.4 kcal/mol for PON and PIN, respectively. The computational studies reveal that the presence of the Zn -bound water molecule depends on the structural feature of substrates characterized by P=O and P=S, which determines the hydrolytic mechanism and efficiency for the degradation of organophosphorus pesticides by PTE.
Topics: Organophosphorus Compounds; Paraoxon; Parathion; Pesticides; Phosphoric Triester Hydrolases; Water
PubMed: 35586954
DOI: 10.1002/asia.202200439