Cited by (178)
Potential ecotoxicity of substrate-enriched zinc oxide nanoparticles to Physalaemus cuvieri tadpoles
2023, Science of the Total Environment
Although the ecotoxicological effects of ZnO nanoparticles (ZnO NPs) have already been reported in different taxa, little is known about their impacts on amphibians. Thus, we aimed to evaluate the potential effects of exposure of Physalaemus cuvieri tadpoles to substrates enriched with ZnO NPs (and with its ionic counterpart, Zn+2, ZnCl2 – both at 100mg/kg) previously used in the cultivation of Panicum maximum (Guinea grass). We showed that although exposure for 21days did not impact the survival, growth, and development of tadpoles, we noted an increase in the frequency of erythrocyte nuclear abnormalities in the “ZnCl2” and “ZnONP” groups, which was associated with suppression of antioxidant activity in the animals (inferred by SOD and CAT activity and DPPH free radical scavenging capacity). In the tadpoles of the “ZnONP” group, we also noticed a reduction in creatinine and bilirubin levels, alpha-amylase activity, and an increase in alkaline phosphatase activity. But the treatments did not alter the activity of the enzymes lactate dehydrogenase and gamma-glutamyl-transferase and total protein and carbohydrate levels. On the other hand, we report a cholinesterase and hypotriglyceridemic effect in the “ZnCl2” and “ZnONP” groups. Zn bioaccumulation in animals, from ZnO NPs, from Zn+2 released from them, or both, has been associated with causing these changes. Finally, principal component analysis (PCA) and the values of the “Integrated Biomarker Response” index revealed that the exposure of animals to substrates enriched with ZnO NPs caused more pronounced effects than those attributed to its ionic counterpart. Therefore, our study reinforces the need to consider the environmental risks of using these nanomaterials for agricultural purposes for amphibians.
Toxicity assessment of polyethylene microplastics in combination with a mix of emerging pollutants on Physalaemus cuvieri tadpoles
2023, Journal of Environmental Sciences (China)
Studies in recent years have shown that aquatic pollution by microplastics (MPs) can be considered to pose additional stress to amphibian populations. However, our knowledge of how MPs affect amphibians is very rudimentary, and even more limited is our understanding of their effects in combination with other emerging pollutants. Thus, we aimed to evaluate the possible toxicity of polyethylene MPs (PE-MPs) (alone or in combination with a mix of pollutants) on the health of Physalaemus cuvieri tadpoles. After 30 days of exposure, multiple biomarkers were measured, including morphological, biometric, and developmental indices, behavioral parameters, mutagenicity, cytotoxicity, antioxidant and cholinesterase responses, as well as the uptake and accumulation of PE-MPs in animals. Based on the results, there was no significant change in any of the parameters measured in tadpoles exposed to treatments, but induced stress was observed in tadpoles exposed to PE-MPs combined with the mixture of pollutants, reflecting significant changes in physiological and biochemical responses. Through principal component analysis (PCA) and integrated biomarker response (IBR) assessment, effects induced by pollutants in each test group were distinguished, confirming that the exposure of P. cuvieri tadpoles to the PE-MPs in combination with a mix of emerging pollutants induces an enhanced stress response, although the uptake and accumulation of PE-MPs in these animals was reduced. Thus, our study provides new insight into the danger to amphibians of MPs coexisting with other pollutants in aquatic environments.
An Update on Peripheral Blood Extracellular Vesicles as Biomarkers for Parkinson's Disease Diagnosis
Parkinson's disease (PD) is the world's second primary neurodegenerative disease, and the diagnosis and treatment of PD have become mainstream research. Over the past decades, several studies have identified potential biomarkers for diagnosing PD. Among them, extracellular vesicles (EVs) can carry specific biomarkers reflecting the physiological and pathological state of the body. Due to the blood–brain barrier (BBB) limitation, peripheral blood is limited in diagnosing neurodegenerative diseases. With the increasing research on EVs, their ability to pass through BBB indicated that peripheral blood could depict disease status like cerebrospinal fluid (CSF). Peripheral blood is a clinically available sample and has recently been widely used by researchers in various studies. In this review, we summarized previous studies on PD diagnosis biomarkers in peripheral blood EVs and evaluated their diagnostic value. Some EV surface markers were also described, which can extract EVs from specific cell origins. In addition, the combination of several biomarkers demonstrated good diagnostic performance in PD diagnosis compared with a single biomarker, suggesting the focus of future research.(Video) 2-Minute Neuroscience: Acetylcholine
Toxicity assessment of SARS-CoV-2-derived peptides in combination with a mix of pollutants on zebrafish adults: A perspective study of behavioral, biometric, mutagenic, and biochemical toxicity
2023, Science of the Total Environment
The dispersion of SARS-CoV-2 in aquatic environments via the discharge of domestic and hospital sewage has been confirmed in different locations. Thus, we aimed to evaluate the possible impacts of zebrafish (Danio rerio) exposure to SARS-CoV-2 peptide fragments (PSPD-2001, 2002, and 2003) alone and combined with a mix of emerging pollutants. Our data did not reveal the induction of behavioral, biometric, or mutagenic changes. But we noticed an organ-dependent biochemical response. While nitric oxide and malondialdehyde production in the brain, gills, and muscle did not differ between groups, superoxide dismutase activity was reduced in the “PSPD”, “Mix”, and “Mix+PSPD” groups. An increase in catalase activity and a reduction in DPPH radical scavenging activity were observed in the brains of animals exposed to the treatments. However, the “Mix+PSPD” group had a higher IBRv2 value, with NO levels (brain), the reduction of acetylcholinesterase activity (muscles), and the DPPH radical scavenging activity (brain and muscles), the most discriminant factors for this group. The principal component analysis (PCA) and hierarchical clustering analysis indicated a clear separation of the “Mix+PSPD” group from the others. Thus, we conclude that exposure to viral fragments, associated with the mix of pollutants, induced more significant toxicity in zebrafish adults than in others.
From plant scent defense to biopesticide discovery: Evaluation of toxicity and acetylcholinesterase docking properties for Lamiaceae monoterpenes
2023, Crop Protection
Monoterpenes are a highly diverse group of chemical scents that originate from plant secondary metabolic processes, one purpose of which is to serve as a defense against herbivores. Plant-derived monoterpenes produced from Lamiaceae species have demonstrated acaricidal activity against pest mites and ticks. However, the mechanism by which these compounds carry out the demise of this group of arachnids is poorly understood. Here, we review the chemistry and bioactivity of these promising compounds and subsequently assess their potential toxicity to mites and ticks through measurement of their docking ability to amino acid residues of the binding pocket of Drosophila melanogaster acetylcholinesterase (AChE). We identified 27 monoterpenes of the Lamiaceae family from the literature that were effective against mite (Varroidae, Tetranychidae, Eriophyidae) and tick (Ixodidae) species that are problematic in agricultural production. Screening of these compounds showed that monoterpenoids possessing methyl groups, such as carvacrol, linalool, α-terpineol, bornyl acetate, and terpine-4-ol, strongly bind to D. melanogaster AChE. Linalool, which fits into the binding pocket in the amino acid catalytic triad of AChE (oxyanion hole residues, hydrogen bond interaction with GLU 237, and anionic binding with TRP 83), was identified as the most promising target for further optimization studies. We propose that monoterpenes which interact strongly with amino acid residues of the AChE receptor be targeted for development of effective, naturally produced biocontrol pesticides, as this model demonstrates potential for discovery of new acaricide compounds in a high throughput manner.
Exposure to polystyrene nanoplastics induces an anxiolytic-like effect, changes in antipredator defensive response, and DNA damage in Swiss mice
2023, Journal of Hazardous Materials
Although the in vivo toxicity of nanoplastics (NPs) has already been reported in different model systems, their effects on mammalian behavior are poorly understood. Thus, we aimed to evaluate whether exposure to polystyrene (PS) NPs (diameter: 23.03±0.266nm) alters the behavior (locomotor, anxiety-like and antipredator) of male Swiss mice, induces brain antioxidant activity, and erythrocyte DNA damage. For this, the animals were exposed to NPs for 20 days at different doses (6.5ng/kg and 6500ng/kg). Initially, we did not observe any effect of pollutants on the locomotor activity of the animals (inferred via open field test and Basso mouse scale for locomotion). However, we noticed an anxiolytic-like behavior (in the open field test) and alterations in the antipredatory defensive response of mice exposed to PS NPs, when confronted with their predator potential (snake, Pantherophis guttatus). Furthermore, such changes were associated with suppressing brain antioxidant activity, inferred by lower DPPH radical scavenging activity, reduced total glutathione content, as well as the translocation and accumulation of NPs in the brain of the animals. In addition, we noted that the treatments induced DNA damage, evaluated via a single-cell gel electrophoresis assay (comet assay) applied to circulating erythrocytes of the animals. However, we did not observe a dose-response effect for all biomarkers evaluated and the estimated accumulation of PS NPs in the brain. The values of the integrated biomarker response index and the results of the principal component analysis (PCA) and the hierarchical clustering analysis confirmed the similarity between the responses of animals exposed to different doses of PS NPs. Therefore, our study sheds light on how PS NPs can impact mammals and reinforce the ecotoxicological risk associated with the dispersion of these pollutants in natural environments and their uptake by mammals.
Recommended articles (6)
Tacrine: In vivo veritas
Pharmacological Research, Volume 116, 2017, pp. 29-31
Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia. Tacrine was also used alone for treating acute anticholinergic syndrome in the 1980s. Shortly after this, it was hypothesised by William Summers that it could be of benefit in treating the early stages of Alzheimer’s dementia and an IND was granted by the US Food and Drug Administration and a use patent awarded to Summers. It was the first of four anticholinesterases to be approved for treating this condition although its variable pharmacokinetics was a disadvantage.
Spintronic characteristics of self-assembled neurotransmitter acetylcholine molecular complexes enable quantum information processing in neural networks and brain
Chemical Physics Letters, Volume 660, 2016, pp. 189-198
Implementation of liquid state quantum information processing based on spatially localized electronic spin in the neurotransmitter stable acetylcholine (ACh) neutral molecular radical is discussed. Using DFT quantum calculations we proved that this molecule possesses stable localized electron spin, which may represent a qubit in quantum information processing.
The necessary operating conditions for ACh molecule are formulated in self-assembled dimer and more complex systems.(Video) Acetylcholinesterase Enzyme
The main quantum mechanical research result of this paper is that the neurotransmitter ACh systems, which were proposed, include the use of quantum molecular spintronics arrays to control the neurotransmission in neural networks.
A newly emerging trend of chitosan-based sensing platform for the organophosphate pesticide detection using Acetylcholinesterase- a review
Trends in Food Science & Technology, Volume 85, 2019, pp. 78-91
Organophosphate pesticides have been extensively used to protect the agricultural produce from being damaged by the pests while growing and the subsequent degradation in its quality. However, in the process of doing so, the pesticides and their degradation products, enter the soil and water and start accumulating in the food products. On the consumption of such pesticide infected food products, Acetylcholinesterase is inhibited, which can be potentially damaging to the central nervous system of human beings. Acetylcholinesterase plays a pivotal role in the orderly functioning of the nervous system and in case of its failure to do so; there is a plausibility of deteriorating health in the individual.
This review gives an insight into the recent approaches towards the rapid sensing of the deleterious pesticides. Numerous sensing platforms, comprising of chitosan as the key element of the immobilization matrix for the subsequent binding of acetylcholinesterase have been highlighted in this study. Chitosan plays the decisive role by aiding in the maintenance of the activity of immobilized Acetylcholinesterase.
The acetylcholinesterase enzyme-inhibition based biosensors pave the way for a speedy and feasible detection of the organophosphate pesticides present in the food articles by bypassing the copious pre-treatments. They also carry the possibility to be used for the real-life sample analysis. Thus, various transducers have been used in combination with the biopolymer chitosan, to produce highly sensitive biosensors for the detection of even trace amounts of these pesticides efficiently.
Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer's disease
European Journal of Medicinal Chemistry, Volume 132, 2017, pp. 294-309
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders with notable factor of dysfunction in cholinergic system. Low ACh level can be observed in the pathogenesis of AD. Several AChE inhibitors have already been used for clinical treatments. However, other than normal conditions, ACh is mostly hydrolyzed by BuChE in progressed AD. Account for an increased level of BuChE and decreased level of AChE in the late stage of AD, development of selective BuChE inhibitor is of vital importance. Up till now, compounds with various scaffolds have been discovered to selectively inhibit BuChE. Different effective anti-BuChE molecules are concluded in this review.(Video) Acetylcholinesterase functions ans structure
The biological activities of butyrylcholinesterase inhibitors
Biomedicine & Pharmacotherapy, Volume 146, 2022, Article 112556
Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
Flavonoids as acetylcholinesterase inhibitors: Current therapeutic standing and future prospects
Biomedicine & Pharmacotherapy, Volume 101, 2018, pp. 860-870
Acetylcholinesterase (AChE), a serine hydrolase, is primarily responsible for the termination of signal transmission in the cholinergic system, owing to its outstanding hydrolyzing potential. Its substrate acetylcholine (ACh), is a neurotransmitter of the cholinergic system, with a predominant effect on motor neurons involved in memory formation. So, by decreasing the activity of this enzyme by employment of specific inhibitors, a number of motor neuron disorders such as myasthenia gravis, glaucoma, Lewy body dementia, and Alzheimer’s disease, among others, can be treated. However, the current-available AChE inhibitors have several limitations in terms of efficacy, therapeutic range, and safety.
Primarily due to the non-compliance of current therapies, new, effective and safe inhibitors are being searched for, especially those which act through multiple receptor sites, but do not elicit undesirable effects. In this regard, the evaluation of phytochemicals such as flavonoids, can be a rational approach. The therapeutic potential of flavonoids has already been recognized agaisnt several ailments. This review deals with various plant-derived flavonoids, their preclinical potential as AChE inhibitors, in established assays, possible mechanisms of action, and structural activity relationship (SAR).(Video) Basic function of the acetylcholinesterase enzyme.
Subsequently, a number of plant-derived flavonoids with outstanding efficacy and potency as AChE inhibitors, the mechanistic, their safety profiles, and pharmacokinetic attributes have been discussed. Through derivatization of these reported flavonoids, some limitation in efficacy or pharmacokinetic parameters can be addressed. The selected flavonoids ought to be tested in clinical studies to discover new neuro-therapeutic candidates.
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