Neurotoxic Compounds Research Articles

Early-life exposure to permethrin affects phenotypic traits in both larval and adult mangrove rivulus Kryptolebias marmoratus

In fishes, the impacts of environmental constraints undergone during development on the behavioural response of individuals are not well understood. Obtaining more information is important since the aquatic environment is widely exposed to pollution involving neurotoxic compounds likely to cause phenotypic changes that can affect animal fitness. We explored how early exposure to the pyrethroid insecticide permethrin (PM), a compound known for its neurotoxicity, influences the phenotypic traits in both larvae and adults of the self-fertilizing fish mangrove rivulus, Kryptolebias marmoratus. First, we investigated immediate effects of PM on larvae after one-week exposure (0–7 days post-hatching): larvae exposed to high concentration (200 µg.L−1) grew less, were less active, had negative thigmotaxis and were less likely to capture prey than control individuals and those exposed to low concentration (5 µg.L−1). No difference was found between treatments when considering oxygen consumption rate and cortisol levels. Persistent effects of early exposure to PM on adults (147–149 days post-hatching) showed that fish previously exposed to high concentration of PM overcompensated growth, leading them to finally be longer and heavier than fish from other treatments. Moreover, we evidenced that levels of cortisol interacted with early PM exposure to affect behaviours during dyadic contests. Fish were more likely to initiate fighting behaviours and were more likely to be aggressive when they have low pre-contest levels of cortisol, but these effects were less pronounced when individuals were exposed to PM. This study shows that PM can have both immediate and persistent effects on phenotypic traits in a self-fertilizing vertebrate and suggests that a pyrethroid can interact with hormones action to affect animal behaviour.

The Acute Effects and Mechanism of Ketamine on Nicotine-Induced Neurogenic Relaxation of the Corpus Cavernosum in Mice.

The present study aimed to investigate the acute effects and the mechanism of ketamine on nicotine-induced relaxation of the corpus cavernosum (CC) in mice. This study measured the intra-cavernosal pressure (ICP) of male C57BL/6 mice and the CC muscle activities using an organ bath wire myograph. Various drugs were used to investigate the mechanism of ketamine on nicotine-induced relaxation. Direct ketamine injection into the major pelvic ganglion (MPG) inhibited MPG-induced increases in ICP. D-serine/L-glutamate-induced relaxation of the CC was inhibited by MK-801 (N-methyl-D-aspartate (NMDA) receptor inhibitor), and nicotine-induced relaxation was enhanced by D-serine/L-glutamate. NMDA had no effect on CC relaxation. Nicotine-induced relaxation of the CC was suppressed by mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist), lidocaine, guanethidine (an adrenergic neuronal blocker), Nw-nitro-L-arginine (a non-selective nitric oxide synthase inhibitor), MK-801, and ketamine. This relaxation was almost completely inhibited in CC strips pretreated with 6-hydroxydopamine (a neurotoxic synthetic organic compound). Ketamine inhibited cavernosal nerve neurotransmission via direct action on the ganglion and impaired nicotine-induced CC relaxation. The relaxation of the CC was dependent on the interaction of the sympathetic and parasympathetic nerves, which may be mediated by the NMDA receptor.

Selective Colorimetric Detection of Novichok Agents with Hydrazone Chemosensors.

Novichok is a recently identified class of neurotoxic organophosphorus compounds that have subsequently been banned by the Organization for Prohibition of Chemical Weapons (OPCW) as chemical warfare agents. Selective, rapid detection of Novichok remains a challenge. Several colorimetric paper-based detection devices have recently been developed for the rapid and selective detection of sarin, VX, and sulfur mustard. In this article, we present a similar colorimetric device designed specifically for the detection of Novichok, based on hydrazone derivatives from 2,4-dinitrophenylhydrazine (2,4-DNPH) impregnated on a glass fiber substrate. Results show that these compounds rapidly and selectively reveal the presence of Novichok agents to the naked eye. The low cost, ease of use, portability, and high selectivity to Novichok of this device complete the detection range of colorimetric paper-based sensors for chemical warfare agents.

A novel automated method for the simultaneous detection of breathing frequency and amplitude in zebrafish (Danio rerio) embryos and larvae

Stress responses of fish to disruption of oxygen homeostasis include adjusted oxygen consumption rate (MO2) as well as the hyperventilation consisting of changes in breathing frequency (fv) and amplitude (fampl). However, studying the HVR in very small organisms such as zebrafish (Danio rerio) embryos and larvae is challenging, and breathing movements (i.e., fv) are usually manually counted, which is time- and human resource-intense, error-prone and does not provide information on the amplitude of breathing movements of the response, the breathing amplitude (fampl). Hence, in the present study, a new automated method was developed to simultaneously measure fv and fampl in small zebrafish embryos and larvae with the computer software DanioScope™. To compare HVR strategies at different life-stages of zebrafish and the physiologically linked MO2, hatched 4 d old embryos and early gill-breathing 12 d old larvae were treated with the HVR-inducing neurotoxic compound lindane (γ-hexachlorocyclohexane; γ-HCH) as a model substance. Comparison of manually counted fv with fv data measured by DanioScope™ at both life-stages showed high to moderate agreement between the two methods with respect to fv in control fish and in fish treated with lower lindane concentrations (3 - 18% deviation at 25 µg/L γ-HCH). With increasing lindane concentrations (100 and 400 µg/L γ-HCH), however, manual counts showed an average underestimation of fv by up to 30%, mainly due to very fast, rapidly successive, and indistinct movements of the fish, which cannot be properly detected by manual counts. Automated measurement thus proved significantly more sensitive, although several pre- and post-processing steps are needed. The improved automated detection of fv and the first reliable estimation of fampl in small fish embryos and larvae, as well as the inclusion of MO2, may provide new insights into different respiratory strategies and may, thus, represent a tool to lower the detection limit for reactions of different life-stages of fish to environmental stressors. In the present study, this became evident, as early gill-breathing 12 d old zebrafish larvae showed symptoms of respiratory failure (i.e., increase in fv, fampl and MO2, followed by subsequent lethargy) after exposure to lindane, whereas skin-breathing in 4 d old embryos proved mainly insensitive to the paralytic effects of lindane.

Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.

Cerebral endothelial cells and their linking tight junctions form a unique, dynamic and multi-functional interface, the blood-brain barrier (BBB). The endothelium is regulated by perivascular cells and components forming the neurovascular unit. This review examines BBB and neurovascular unit changes in normal aging and in neurodegenerative disorders, particularly focusing on Alzheimer disease, cerebral amyloid angiopathy and vascular dementia. Increasing evidence indicates BBB dysfunction contributes to neurodegeneration. Mechanisms underlying BBB dysfunction are outlined (endothelium and neurovascular unit mediated) as is the BBB as a therapeutic target including increasing the uptake of systemically delivered therapeutics across the BBB, enhancing clearance of potential neurotoxic compounds via the BBB, and preventing BBB dysfunction. Finally, a need for novel biomarkers of BBB dysfunction is addressed.

Contributions of blood-brain barrier imaging to neurovascular unit pathophysiology of Alzheimer's disease and related dementias.

The blood-brain barrier (BBB) plays important roles in the maintenance of brain homeostasis. Its main role includes three kinds of functions: (1) to protect the central nervous system from blood-borne toxins and pathogens; (2) to regulate the exchange of substances between the brain parenchyma and capillaries; and (3) to clear metabolic waste and other neurotoxic compounds from the central nervous system into meningeal lymphatics and systemic circulation. Physiologically, the BBB belongs to the glymphatic system and the intramural periarterial drainage pathway, both of which are involved in clearing interstitial solutes such as β-amyloid proteins. Thus, the BBB is believed to contribute to preventing the onset and progression for Alzheimer's disease. Measurements of BBB function are essential toward a better understanding of Alzheimer's pathophysiology to establish novel imaging biomarkers and open new avenues of interventions for Alzheimer's disease and related dementias. The visualization techniques for capillary, cerebrospinal, and interstitial fluid dynamics around the neurovascular unit in living human brains have been enthusiastically developed. The purpose of this review is to summarize recent BBB imaging developments using advanced magnetic resonance imaging technologies in relation to Alzheimer's disease and related dementias. First, we give an overview of the relationship between Alzheimer's pathophysiology and BBB dysfunction. Second, we provide a brief description about the principles of non-contrast agent-based and contrast agent-based BBB imaging methodologies. Third, we summarize previous studies that have reported the findings of each BBB imaging method in individuals with the Alzheimer's disease continuum. Fourth, we introduce a wide range of Alzheimer's pathophysiology in relation to BBB imaging technologies to advance our understanding of the fluid dynamics around the BBB in both clinical and preclinical settings. Finally, we discuss the challenges of BBB imaging techniques and suggest future directions toward clinically useful imaging biomarkers for Alzheimer's disease and related dementias.

Structural and Functional Analysis of a Highly Active Designed Phosphotriesterase for the Detoxification of Organophosphate Nerve Agents Reveals an Unpredicted Conformation of the Active Site Loop.

Neurotoxic organophosphorus compounds (OPs) pose a severe threat if misused in military conflicts or by terrorists. Administration of a hydrolytic enzyme that can decompose the circulating nerve agent into non-toxic metabolites in vivo offers a potential treatment. A promising candidate is the homo-dimeric phosphotriesterase originating from the bacterium Brevundimonas diminuta (BdPTE), which has been subject to several rational and combinatorial protein design studies. A series of engineered versions with much improved catalytic efficiencies toward medically relevant nerve agents was described, carrying up to 22 mutations per enzyme subunit. To provide a basis for further rational design, we have determined the crystal structure of the highly active variant 10-2-C3(C59V/C227V)─stabilized against oxidation by substitution of two unpaired Cys residues─in complex with a substrate analogue at 1.5 Å resolution. Unexpectedly, the long loop segment (residues 253-276) that covers the active site shows a totally new conformation, with drastic structural deviations up to 19 Å, which was neither predicted in any of the preceding protein design studies nor seen in previous crystallographic analyses of less far evolved enzyme versions. Inspired by this structural insight, additional amino acid exchanges were introduced and their effects on protein stability as well as on the catalytic efficiency toward several neurotoxic OPs were investigated. Somewhat surprisingly, our results suggest that the presently available engineered version of BdPTE, in spite of its design on the basis of partly false structural assumptions, constitutes a fairly optimized enzyme for the detoxification of relevant OP nerve agents.

Fused human paraoxonase 1 as a prophylactic agent against organophosphate poisoning

Organophosphates (OPs) are highly neurotoxic compounds and certain OP-compounds are also exploited as a weapon of mass destruction and chemical warfare in terrorist attacks. Available prophylactic and post-exposure treatments are less effective and also have serious side-effects. Thus, there is a dire need to develop effective and safe prophylactic agent(s) against OP-poisoning. Human Paraoxonase 1 (hPON1) can hydrolyze a wide range of OP molecules and can be developed as an effective and safe prophylactic agent. Thus, there is a dire need in the art to develop variant(s) of rhPON1 that not only possess ‘good’ OP-hydrolyzing activity but also have improved pharmacokinetic properties. In this report, we describe the characterization of the fused hPON1 (FHP) variant that not only exhibit enhanced in vivo pharmacokinetic properties but also delay / prevent the symptoms of OP-poisoning and prevents OP-induced mortality in rats.

A Comparison of Acrylamide Contents of Some Nuts Produced Organically and Conventionally

Acrylamide is a carcinogenic and neurotoxic compound defined as a heat treatment process contaminant. Due to its health concern, acrylamide formation needed to be minimized. The objective of this study is to examine how much acrylamide is contained in dried almonds (Prunus dulcis), hazelnuts (Corylus avellana), pistachios (Pistacia vera), peanuts (Arachishypogaea), sunflower seeds (Helianthus annuus) as well as pumpkin seeds (Cucurbita pepo) that have been cultivated via organically-certified and conventional processes. Frequently and regularly-consumed nuts - comprising 180 samples that have been cultivated via organically-certified and conventional processes - were studied with UHPLC-MS/MS approach in Turkey. Substantial disparities were statistically found (P

Automated and fast online method for simultaneously determining a broad spectrum of per- and polyfluoroalkyl substances in a small volume of cerebrospinal fluid.

Per- and polyfluoroalkyl substances (PFASs) are potentially neurotoxic compounds. Levels of PFASs in cerebrospinal fluid (CSF) could directly reflect their potential harm to the central nervous system. Because of the variety of PFASs and the rarity of CSF, there is an urgent need to establish a rapid online method to detect a broad spectrum of PFASs accurately and simultaneously by consuming a small amount of CSF. In this study, we developed a fast and automated method to analyze 52 PFASs in human CSF samples using online TurboFlow ultra-high-performance liquid chromatography-tandem mass spectrometry. Our method offered excellent matrix-matched standard curve linearity (correlation coefficient > 0.99), good limits of quantitation (MLOQs) (0.01 to 0.08 ng mL-1), satisfactory accuracy (recoveries of 74.6%-119.1%) and precision (relative standard deviations of 1.4%-13.2%), small sample amount consumption (50 μL), and fast analysis time (18 min per sample) without complex sample pretreatment procedures. These are advantageous for the high throughput screening of PFASs in environmental epidemiology studies. Repeated freeze-thaw experiments showed that it was better to perform the analytical process soon as possible after sample collection. The established method was used to analyze PFASs in 60 people. Short-chain PFASs, perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and novel PFASs [sodium 2-(N-ethylperfluorooctane-1-sulfonamido)ethyl phosphate (SAmPAP), perfluoroethylcyclohexanesulfonate (PFECHS), and perfluoro-3, 7-dimethyloctanoic acid (P37DMOA)] were reported in CSF for the first time. PFBA and PFPeA were detected in all samples with mean concentrations of 0.24 and 0.22 ng mL-1, respectively. We also calculated the blood-brain barrier transmission efficiency of PFASs (RPFAS), and the mean RPFBA value was above 1, which indicated that PFBA might transfer from serum to CSF.

Drosophila melanogaster as an indispensable model to decipher the mode of action of neurotoxic compounds

Exposure to some toxic compounds causes structural and behavioral anomalies associated with the neurons in the later stage of life. Those toxic compounds are termed as a neurotoxicant, which can be a physical factor, a toxin, an infection, radiation, or maybe a drug. The incongruities caused due to a neurotoxicant further depend on the toxicity of the compound. More importantly, the neurotoxicity of the compound is associated with the concentration and the time point of exposure. The neurodevelopmental defect appears depending on the toxicity of the compound. A neurodevelopmental defect may be associated with a delay in developmental time, defective growth, structural abnormality of many organs, including sensory organs, behavioral abnormalities, or death in the fetus stage. Numerous model organisms are employed to assess the effect of neurotoxicants. The current review summarizes several methods used to check the effect of neurotoxicant and their effect using the model organism Drosophila melanogaster.

Machine Learning Modeling and Insights into the Structural Characteristics of Drug-Induced Neurotoxicity.

Neurotoxicity can be resulted from many diverse clinical drugs, which has been a cause of concern to human populations across the world. The detection of drug-induced neurotoxicity (DINeurot) potential with biological experimental methods always required a lot of budget and time. In addition, few studies have addressed the structural characteristics of neurotoxic chemicals. In this study, we focused on the computational modeling for drug-induced neurotoxicity with machine learning methods and the insights into the structural characteristics of neurotoxic chemicals. Based on the clinical drug data with neurotoxicity effects, we developed 35 different classifiers by combining five different machine learning methods and seven fingerprint packages. The best-performing model achieved good results on both 5-fold cross-validation (balanced accuracy of 76.51%, AUC value of 0.83, and MCC value of 0.52) and external validation (balanced accuracy of 83.63%, AUC value of 0.87, and MCC value of 0.67). The model can be freely accessed on the web server DINeuroTpredictor (http://dineurot.sapredictor.cn/). We also analyzed the distribution of several key molecular properties between neurotoxic and non-neurotoxic structures. The results indicated that several physicochemical properties were significantly different between the neurotoxic and non-neurotoxic compounds, including molecular polar surface area (MPSA), AlogP, the number of hydrogen bond acceptors (nHAcc) and donors (nHDon), the number of rotatable bonds (nRotB), and the number of aromatic rings (nAR). In addition, 18 structural alerts responsible for chemical neurotoxicity were identified. The structural alerts have been integrated with our web server SApredictor (http://www.sapredictor.cn). The results of this study could provide useful information for the understanding of the structural characteristics and computational prediction for chemical neurotoxicity.

Regulation of P-Glycoprotein in the Brain

Maintenance of the tightly regulated homeostatic environment of the brain is facilitated by the blood-brain barrier (BBB). P-glycoprotein (P-gp), an ATP-binding cassette transporter, is expressed on the luminal surface of the endothelial cells in the BBB, and actively exports a wide variety of substrates to limit exposure of the vulnerable brain environment to waste buildup and neurotoxic compounds. Downregulation of P-gp expression and activity at the BBB have been reported with ageing and in neurodegenerative diseases. Upregulation of P-gp at the BBB contributes to poor therapeutic outcomes due to altered pharmacokinetics of CNS-acting drugs. The regulation of P-gp is highly complex, but unravelling the mechanisms involved may help the development of novel and nuanced strategies to modulate P-gp expression for therapeutic benefit. This review summarises the current understanding of P-gp regulation in the brain, encompassing the transcriptional, post-transcriptional and post-translational mechanisms that have been identified to affect P-gp expression and transport activity.

Zebrafish: A Pharmacological Model for Learning and Memory Research.

Learning and memory are essential to organism survival and are conserved across various species, especially vertebrates. Cognitive studies involving learning and memory require using appropriate model organisms to translate relevant findings to humans. Zebrafish are becoming increasingly popular as one of the animal models for neurodegenerative diseases due to their low maintenance cost, prolific nature and amenability to genetic manipulation. More importantly, zebrafish exhibit a repertoire of neurobehaviors comparable to humans. In this review, we discuss the forms of learning and memory abilities in zebrafish and the tests used to evaluate the neurobehaviors in this species. In addition, the pharmacological studies that used zebrafish as models to screen for the effects of neuroprotective and neurotoxic compounds on cognitive performance will be summarized here. Lastly, we discuss the challenges and perspectives in establishing zebrafish as a robust model for cognitive research involving learning and memory. Zebrafish are becoming an indispensable model in learning and memory research for screening neuroprotective agents against cognitive impairment.

Thiamethoxam in soybean seed treatment: Plant bioactivation and hormesis, besides whitefly control?

Amid concerns on the myriad of existing chemical stressors in agroecosystems, pesticides and particularly neonicotinoid insecticides are in the forefront. Despite that, these neurotoxic compounds remain the dominant group of insecticides in worldwide use with the added versatility of use in seed coatings. Such use sparks environmental concerns counterbalanced by their reported insecticidal efficacy and potential plant bioactivation. Nonetheless, this alleged double benefit and interconnection expected with neonicotinoids has been little explored particularly when the whole plant phenology is considered. Regardless of the expected efficacy against targeted insect pest species, like whiteflies, neonicotinoids may spark dual effect on plants – negative at higher concentrations, positive at low concentrations, which is consistent with the hormesis phenomenon that may be expressed as a plant bioactivation. This effect may also cascade to the targeted insect species, what deserves attention. Therefore, soybean seeds treated with increasing concentrations of the neonicotinoid thiamethoxam were followed throughout their development in greenhouse, recording the plant response and yield, besides their effect in whiteflies (Bemisia tabaci MEAM1). Thiamethoxam application was correlated to leaf contents of thiamethoxam and its metabolite clothianidin. Plant hormesis was found for leaf area and root growth, but not for other plant morphological or physiological parameters, nor plant yield. The insecticide concentration-dependency compromised whitefly population growth without evidence of cascading any plant-mediated hormesis to the insects. Thus, although plant hormesis was recognized with thiamethoxam in treated soybean seeds in relevant parameters, no evidence of plant bioactivation was observed to justify its use with such a secondary objective, nor did this hormesis impair whitefly control.

Digoxin Induces Human Astrocyte Reaction In Vitro

Astrocyte reaction is a complex cellular process involving astrocytes in response to various types of CNS injury and a marker of neurotoxicity. It has been abundantly studied in rodents but relatively poorly in human cells due to limited access to the brain. Astrocytes play important roles in cerebral energy metabolism and are also key players in neuroinflammation. Astroglial metabolic and inflammatory changes have been reported with age, leading to the hypothesis that mitochondrial metabolism and inflammatory responses are interconnected. However, the relationship between energy metabolism and astrocyte reactivity in the context of neurotoxicity is not known. We hypothesized that changes in energy metabolism of astrocytes will be coupled to their activation by xenobiotics. Astrocyte reaction and associated energy metabolic changes were assessed by immunostaining, gene expression, proteomics, metabolomics, and extracellular flux analyses after 24 h of exposure of human ReN-derived astrocytes to digoxin (1–10 µM) or TNFα (30 ng/ml) used as a positive control. Strong astrocytic reaction was observed, accompanied by increased glycolysis at low concentrations of digoxin (0.1 and 0.5 µM) and after TNFα exposure, suggesting that increased glycolysis may be a common feature of reactive astrocytes, independent of the triggering molecule. In conclusion, whether astrocyte activation is triggered by cytokines or a xenobiotic, it is strongly tied to energy metabolism in human ReN-derived astrocytes. Increased glycolysis might be considered as an endpoint to detect astrocyte activation by potentially neurotoxic compounds in vitro. Finally, ReN-derived astrocytes may help to decipher mechanisms of neurotoxicity in ascertaining the ability of chemicals to directly target astrocytes.

Identification of neurotoxic compounds in cyanobacteria exudate mixtures

Release of toxic cyanobacterial secondary metabolites threatens biosecurity, foodwebs and public health. Microcystis aeruginosa (Ma), the dominant species in global freshwater cyanobacterial blooms, produces exudates (MaE) that cause adverse outcomes including nerve damage. Previously, we identified > 300 chemicals in MaE. It is critical to investigate neurotoxicity mechanisms of active substances among this suite of Ma compounds. Here, we screened 103 neurotoxicity assays from the ToxCast database to reveal targets of action of MaE using machine learning. We then built a potential Adverse Outcome Pathway (AOP) to identify neurotoxicity mechanisms of MaE as well as key targets. Finally, we selected potential neurotoxins matched with those targets using molecular docking. We found 38 targets that were inhibited and eight targets that were activated, collectively mainly related to neurotransmission (i.e. cholinergic, dopaminergic and serotonergic neurotransmitter systems). The potential AOP of MaE neurotoxicity could be caused by blocking calcium voltage-gated channel (CACNA1A), because of antagonizing neurotransmitter receptors, or because of inhibiting solute carrier transporters. We identified nine neurotoxic MaE compounds with high affinity to those targets, including LysoPC(16:0), 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, egonol glucoside, polyoxyethylene (600) monoricinoleate, and phytosphingosine. Our study enhances understanding of neurotoxicity mechanisms and identifies neurotoxins in cyanobacterial bloom exudates, which may help identify priority compounds for cyanobacteria management.

Acrylamide in human breast milk - the current state of knowledge.

Human milk is a first choice in infant nutrition. It not only provides all the nutrients necessary for the proper infant`s development but also contains bioactive factors that provide natural protection against infections. Unfortunately, chemical contaminants can pass to breast milk and pose a health risk for the breastfed infant's health. Acrylamide is a typical process contaminant and in food it is formed as a result of the Maillard reaction. Numerous studies have shown that acrylamide is a neurotoxic and carcinogenic compound. So far there have been published only three studies on the acrylamide content in human milk. In two of them, the acrylamide level in most of the tested samples did not exceed the value of 0.5 μg/L. In the third study, the authors assessed the circulation of acrylamide in the body of two breastfeeding women after consuming products with high acrylamide content. Depending on the time elapsed after the meal, the acrylamide content ranged from 3.17 μg/L to 18.8 μg /L. These studies show that the breastfeeding mothers' diet may have a significant influence on the level of acrylamide in their milk. However, it seems that the acrylamide content in breast milk is also influenced by the time of breast milk collection, including the time elapsed after the mother's meal. To assess the exposure of breastfed infants to acrylamide in human milk, more data is needed on the acrylamide content in human milk at different stages of lactation and using standard protocols for human milk sampling.

Botulinum toxin A in abdominal wall reconstruction for incisional hernia: an interesting line of research in abdominal wall and plastic surgery

Botulinum toxin A in abdominal wall reconstruction for incisional hernia: an interesting line of research in abdominal wall and plastic surgery

Acrylamide; a neurotoxin in popcorns: a systematic review and meta-analysis.

Acrylamide is a known neurotoxic compound for humans. Foods that have high concentrations of acrylamide need to be identified. One of the food products containing acrylamide is popcorn. Popcorn is an important source of snacks for children, especially students. The presented study is a systematic review and meta-analysis of the level ofacrylamide in popcorn. The search was done in different databases with the keywords; acrylamide, popcorn, popped corn. 27 articles were found by searching various databases. After initial screening and full text evaluation, 8 articles were selected for systematic review and 6 articles for meta-analysis. The amount of acrylamide in this product was inthe range of 1,017.7-106μg/kg. Microwaved corn contains lower amounts of acrylamide than other methods of preparation. The type of popcorn also had an effect on the amount of acrylamide with Meta-regression. It was found that sweet popcorn contains higher amounts of acrylamide. The overall value of acrylamide concentration inpopcorns was calculated to be 459.6±220.3μg/kg. This amount is high and requires measures to reduce the amount of acrylamide.