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Harmful Algae Feb 2020Anatoxin-a(S) is the most potent natural neurotoxin produced by fresh water cyanobacteria. It is also the least understood and monitored. Although this potent...
Anatoxin-a(S) is the most potent natural neurotoxin produced by fresh water cyanobacteria. It is also the least understood and monitored. Although this potent cholinesterase inhibitor was first reported in the 1970s and connected with animal poisonings, the lack of chemical standards and identified biosynthetic genes together with limited diagnostics and acute reactivity of this naturally-occurring organophosphate have limited our understanding of its environmental breadth and human health implications. Anatoxin-a(S) irreversibly inhibits acetylcholinesterase much like other organophosphate agents like paraoxon. It is however often confused with the similarly named anatoxin-a that has a completely different chemical structure, mechanism of action, and biosynthesis. Herein we propose renaming of anatoxin-a(S) to clarify its distinct structure and mechanism and to draw renewed attention to this potent natural poison. We propose the new name guanitoxin (GNT) to emphasize its distinctive guanidino organophosphate chemical structure.
Topics: Animals; Cholinesterase Inhibitors; Cyanobacteria; Fresh Water; Humans; Neurotoxins; Organophosphates
PubMed: 32113603
DOI: 10.1016/j.hal.2019.101737 -
ACS Nano Jun 2019The lack of pharmaceutical antidotes for deadly toxicants has motivated tremendous research interests in seeking synthetic nanoscavengers to absorb and neutralize...
The lack of pharmaceutical antidotes for deadly toxicants has motivated tremendous research interests in seeking synthetic nanoscavengers to absorb and neutralize harmful biological or chemical agents. Herein, we report a cell-membrane-cloaked oil nanosponge formulation capable of dual-modal detoxification. The biomimetic oil nanosponge consists of an olive oil nanodroplet wrapped by a red blood cell membrane. In such a construct, the oil core can nonspecifically soak up toxicants through physical partition and the cell membrane shell can specifically absorb and neutralize toxicants through biological binding. The dual-modal detoxification capability of the oil nanosponges was validated using three distinct organophosphates (OPs), including paraoxon, diisopropyl fluorophosphate, and dichlorvos. By inhibiting acetylcholinesterase, OPs cause the accumulation of acetylcholine, which leads to neuromuscular disorders and even death. In mouse models of OP poisoning, the oil nanosponges reduced clinical signs of OP intoxication, lowered OP concentration in tissues, and greatly enhanced mouse survival in both the therapeutic regimen and the prophylactic regimen. Overall, oil nanosponges combine the merits of both cell membrane and oil nanodroplets for safe and effective detoxification, which also serve as a prototype of multimodal detoxification platforms.
Topics: Absorption, Physicochemical; Acetylcholinesterase; Animals; Antidotes; Cell Membrane; Cholinesterase Inhibitors; Erythrocytes; Mice; Mice, Inbred ICR; Nanoparticles; Olive Oil; Organophosphate Poisoning; Organophosphates; Protein Binding
PubMed: 31117372
DOI: 10.1021/acsnano.9b02773 -
Drug and Chemical Toxicology Nov 2022Acute toxicity of organophosphorus compounds is primarily caused by inhibition of acetylcholinesterase (AChE) at cholinergic synapses. The current study was designed to...
Acute toxicity of organophosphorus compounds is primarily caused by inhibition of acetylcholinesterase (AChE) at cholinergic synapses. The current study was designed to investigate the effects of paraoxon on histological changes as well as the role of mitochondrion-dependent apoptosis in causing this damage in the rat cerebellum. Adult male Wistar rats were intraperitoneally injected with paraoxon at 0.3, 0.7, or 1 mg/kg. Control animals were injected with corn oil as a vehicle. At 14 or 28 days after intoxication, histological changes and alterations in the expression of apoptosis-related proteins, including Bax, Bcl-2, and caspase-3, were investigated in the cerebellum using cresyl violet staining and western blotting, respectively. Findings showed the decreased thickness of both molecular and granular layers and reduction in the number of Purkinje cells in animals treated with a higher convulsive dose of paraoxon (1 mg/kg). In addition, exposure of rats to 1 mg/kg of paraoxon activated apoptosis pathway confirmed by an increase in Bax and caspase-3 and a decrease in Bcl-2 protein levels. According to our results, cerebellar histological changes and alterations in the expression of apoptosis-related proteins occur following exposure to a high convulsive dose of paraoxon and persist for a long time.
Topics: Animals; Male; Rats; Acetylcholinesterase; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Cerebellum; Cholinergic Agents; Cholinesterase Inhibitors; Organophosphorus Compounds; Paraoxon; Proto-Oncogene Proteins c-bcl-2; Rats, Wistar
PubMed: 34412520
DOI: 10.1080/01480545.2021.1966243 -
Synthetic and Systems Biotechnology Sep 2021is a commonly used commercial specie with broad applications in the fields of bioengineering and biotechnology. is capable of producing both biofilms and spores.... (Review)
Review
is a commonly used commercial specie with broad applications in the fields of bioengineering and biotechnology. is capable of producing both biofilms and spores. Biofilms are matrix-encased multicellular communities that comprise various components including exopolysaccharides, proteins, extracellular DNA, and poly-γ-glutamic acid. These biofilms resist environmental conditions such as oxidative stress and hence have applications in bioremediation technologies. Furthermore, biofilms and spores can be engineered through biotechnological techniques for environmentally-friendly and safe production of bio-products such as enzymes. The ability to withstand with harsh conditions and producing spores makes a suitable candidate for surface display technology. In recent years, the spores of such specie are widely used as it is generally regarded as safe to use. Advances in synthetic biology have enabled the reprogramming of biofilms to improve their functions and enhance the production of value-added products. Globally, there is increased interest in the production of engineered biosensors, biocatalysts, and biomaterials. The elastic modulus and gel properties of biofilms have been utilized to develop living materials. This review outlines the formation of biofilms and spores. Biotechnological engineering processes and their increasing application in bioremediation and biocatalysis, as well as the future directions of biofilm engineering, are discussed. Furthermore, the ability of biofilms and spores to fabricate functional living materials with self-regenerating, self-regulating and environmentally responsive characteristics has been summarized. This review aims to resume advances in biological engineering of biofilms and spores and their applications.
PubMed: 34401544
DOI: 10.1016/j.synbio.2021.07.002 -
Journal of Hazardous Materials Jun 2022The residues of organophosphorus pesticides have caused the potential risk in environment and human health, arousing worldwidely great concern. Herein, we fabricated a...
The residues of organophosphorus pesticides have caused the potential risk in environment and human health, arousing worldwidely great concern. Herein, we fabricated a robust gold nanoclusters/MnO composites-based hydrogel portable kit for accurate monitoring of paraoxon residues and degradation in Chinese cabbages. With the immobilization of gold nanoclusters/MnO composites into a hydrogel, a ratiometric fluorescent signal is generated by catalyzing the oxidation of o-phenylenediamine, which possesses a built-in correction with low background interference. Coupling with acetylcholinesterase catalytic reactions and pesticide inhibition effect, the portable kit can sensitively detect paraoxon residues with a detection limit of 5.0 ng mL. For on-site quantification, the fluorescent color variations of portable kit are converted into digital information that exhibits applicative linear range toward pesticide. Notably, the hydrogel portable kit was successfully applied for precisely monitoring the residue and degradation of paraoxon in Chinese cabbage, providing a potential pathway toward practical point-of-care testing in food safety monitoring.
Topics: Acetylcholinesterase; Biosensing Techniques; Fluorescent Dyes; Gold; Humans; Hydrogels; Limit of Detection; Manganese Compounds; Organophosphorus Compounds; Oxides; Paraoxon; Pesticides; Point-of-Care Systems
PubMed: 35334266
DOI: 10.1016/j.jhazmat.2022.128660 -
PloS One 2016Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as...
Organophosphates (OPs) are potentially able to affect serine proteases by reacting with their active site. The potential effects of OPs on coagulation factors such as thrombin and on coagulation tests have been only partially characterized and potential interactions with OPs antidotes such as oximes and muscarinic blockers have not been addressed. In the current study, we investigated the in vitro interactions between coagulation, thrombin, the OP paraoxon, and its antidotes obidoxime and atropine. The effects of these substances on thrombin activity were measured in a fluorescent substrate and on coagulation by standard tests. Both paraoxon and obidoxime but not atropine significantly inhibited thrombin activity, and prolonged prothrombin time, thrombin time, and partial thromboplastin time. When paraoxon and obidoxime were combined, a significant synergistic effect was found on both thrombin activity and coagulation tests. In conclusion, paraoxon and obidoxime affect thrombin activity and consequently alter the function of the coagulation system. Similar interactions may be clinically relevant for coagulation pathways in the blood and possibly in the brain.
PubMed: 27689805
DOI: 10.1371/journal.pone.0163787 -
Journal of Hazardous Materials Apr 2022A green approach to produce a cellulose-derived biocatalyst containing hydroxamic acids targeted for the neutralization of toxic organophosphates is shown. The cellulose...
A green approach to produce a cellulose-derived biocatalyst containing hydroxamic acids targeted for the neutralization of toxic organophosphates is shown. The cellulose source, rice husk, is among the largest agricultural waste worldwide and can be strategically functionalized, broadening its sustainable application. Herein, rice husk was oxidized in different degrees, leading to carboxylic acid-based colloidal and solid samples. These were functionalized with hydroxamic acids via amide bonds and fully characterized. The hydroxamic acid derived biocatalysts were evaluated in the cleavage of toxic organophosphates, including the pesticide Paraoxon. Catalytic increments reached up to 10-fold compared to non-catalyzed reactions. Most impressively, the materials showed P atom-selectivity and recyclability features. This guarantees only one reaction pathway that leads to less toxic products, hereby, detoxifies. Overall, highly sustainable catalysts are presented, that benefits from waste source, its green functionalization and is successfully employed for the promotion of chemical security of threatening organophosphates. To the best of our knowledge, this is the first report of a hydroxamate-derived rice husk (selectively modified at the C6 of cellulose) and its application in organophosphates reaction.
Topics: Agriculture; Catalysis; Cellulose; Oryza; Pesticides
PubMed: 34872781
DOI: 10.1016/j.jhazmat.2021.127885 -
Neurobiology of Disease Jan 2020Organophosphate (OP) chemicals include pesticides such as parathion, and nerve gases such as sarin and soman and are considered major chemical threat agents. Acute OP... (Review)
Review
Organophosphate (OP) chemicals include pesticides such as parathion, and nerve gases such as sarin and soman and are considered major chemical threat agents. Acute OP exposure is associated with a cholinergic crisis and status epilepticus (SE). It is also known that the survivors of OP toxicity exhibit neurobehavioral deficits such as mood changes, depression, and memory impairment, and acquired epilepsy. Our research has focused on addressing the need to develop effective therapeutic agents that could be administered even after prolonged seizures and would prevent or lessen the chronic morbidity associated with OP-SE survival. We have developed rat survival models of OP pesticide metabolite paraoxon (POX) and nerve agent sarin surrogate diisopropyl fluorophosphate (DFP) induced SE that are being used to screen for medical countermeasures against an OP attack. Our research has focused on studying neuronal calcium (Ca) homeostatic mechanisms for identifying mechanisms and therapeutics for the expression of neurological morbidities associated with OP-SE survival. We have observed development of a "Ca plateau" characterized by sustained elevations in neuronal Ca levels in OP-SE surviving rats that coincided with the appearance of OP-SE chronic morbidities. These Ca elevations had their origin in Ca release from the intracellular stores such that blockade with antagonists like dantrolene, carisbamate, and levetiracetam lowered OP-SE mediated Ca plateau and afforded significant neuroprotection. Since the Ca plateau lasts for a prolonged period, our studies suggest that blocking it after the control of SE may represent a unique target for development of novel countermeasures to prevent long term Ca mediated OP-SE neuropsychiatric comorbidities such as depression, anxiety, and acquired epilepsy (AE).
Topics: Animals; Brain; Calcium; Depression; Epilepsy; Homeostasis; Memory Disorders; Neurons; Organophosphate Poisoning; Rats; Status Epilepticus
PubMed: 30872159
DOI: 10.1016/j.nbd.2019.03.006 -
Biosensors & Bioelectronics Feb 2019Herein, we propose the first three-dimensional origami paper-based device for the detection of several classes of pesticides by combining different enzyme-inhibition...
Herein, we propose the first three-dimensional origami paper-based device for the detection of several classes of pesticides by combining different enzyme-inhibition biosensors. This device was developed by integrating two different office paper-based screen-printed electrodes and multiple filter paper-based pads to load enzymes and enzymatic substrates. The versatile analysis of different pesticides was carried by folding and unfolding the filter paper-based structure, without any addition of reagents and any sample treatment (i.e. dilution, filtration, pH adjustment). The paper-based platform was employed to detect paraoxon, 2,4-dichlorophenoxyacetic acid, and atrazine by exploiting the capability of these different types of pesticides (i.e. organophosphorus insecticides, phenoxy-acid herbicides, and triazine herbicide) to inhibit butyrylcholinesterase, alkaline phosphatase, and tyrosinase, respectively. The degree of inhibition correlating to the quantity of pesticides was evaluated by chronoamperometrically monitoring the enzymatic activity in the absence and in the presence of pesticides by using a portable potentiostat. To improve the sensitivity, the paper-based electrodes were modified with carbon black alone in the case of platforms for 2,4-dichlorophenoxyacetic acid and atrazine detection, or decorated with Prussian blue nanoparticles for the detection of paraoxon. The paper-based device was applied for the detection of paraoxon, 2,4-dichlorophenoxyacetic acid, and atrazine at ppb level in both standard solutions and river water sample. The accuracy of this origami multiple paper-based electrochemical biosensor was evaluated in river water by recovery studies, obtaining satisfactory values (e.g. for paraoxon 90 ± 1% and 88 ± 2%, for 10 and 20 ppb, respectively). The proposed three-dimensional origami paper device allows for rapid, cost-effective and accurate pesticide detection in surface water as a result of combining filter and office papers, screen-printing, wax-printing and nanomaterial technology.
Topics: 2,4-Dichlorophenoxyacetic Acid; Biosensing Techniques; Humans; Insecticides; Limit of Detection; Organophosphorus Compounds; Paper; Paraoxon; Pesticides; Rivers; Water; Water Pollutants, Chemical
PubMed: 30466052
DOI: 10.1016/j.bios.2018.10.014 -
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