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Exposure of NSCs to low concentrations of PQ and MB in combination does not induce cell death. P1 cells were exposed to PQ (1 μM) and/or to MB (1 μM) for 24 h. Necrotic cells (a) were detected by propidium iodide incorporation assay and the results are expressed as percentage of cell death, where the 100% of cell death value represents control cells treated with 2% Triton X-100 for 5 min. Apoptotic nuclei (b) were detected by using staining with Hoechst 33342 and are expressed as percentage of condensed nuclei. Data are represented as mean ± S.E.M. (n = 4)
Source publication
Pesticide exposure has been linked to the pathogenesis of neurodevelopmental and neurodegenerative disorders including autism spectrum disorders, attention deficit/hyperactivity, and Parkinson’s disease (PD). Developmental exposure to pesticides, even at low concentrations not harmful for the adult brain, can lead to neuronal loss and functional de...
Citations
... They have been discovered in the human placenta and have been linked to increased oxidative stress, intrauterine limitation, and decreased birth weight. In particular, lipid peroxidation (one of the key oxidative stress markers) and cytotoxicity have been observed in humans, primarily in pregnant women and agricultural producers (69). However, studies utilizing pesticides on mammals that directly connect the lethality of the contaminants and oxidative stress are exceedingly rare. ...
Pesticides play a crucial role in modern agriculture, aiding in the protection of crops from pests and diseases. However, their indiscriminate use has raised concerns about their potential adverse effects on human health and the environment. Pesticide residues in food and water supplies are a serious health hazards to the general public since long-term exposure can cause cancer, endocrine disruption, and neurotoxicity, among other health problems. In response to these concerns, researchers and health professionals have been exploring alternative approaches to mitigate the toxic effects of pesticide residues. Bioactive substances called nutraceuticals that come from whole foods including fruits, vegetables, herbs, and spices have drawn interest because of their ability to mitigate the negative effects of pesticide residues. These substances, which include minerals, vitamins, antioxidants, and polyphenols, have a variety of biological actions that may assist in the body’s detoxification and healing of harm from pesticide exposure. In this context, this review aims to explore the potential of nutraceutical interventions as a promising strategy to mitigate the toxic effects of pesticide residues.
... They have been discovered in the human placenta and have been linked to increased oxidative stress, intrauterine limitation, and decreased birth weight. In particular, lipid peroxidation (one of the key oxidative stress markers) and cytotoxicity have been observed in humans, primarily in pregnant women and agricultural producers (69). However, studies utilizing pesticides on mammals that directly connect the lethality of the contaminants and oxidative stress are exceedingly rare. ...
Pesticides play a crucial role in modern agriculture, aiding in the protection of crops from pests and diseases. However, their indiscriminate use has raised concerns about their potential adverse effects on human health and the environment. Pesticide residues in food and water supplies are a serious health hazards to the general public since long-term exposure can cause cancer, endocrine disruption, and neurotoxicity, among other health problems. In response to these concerns, researchers and health professionals have been exploring alternative approaches to mitigate the toxic effects of pesticide residues. Bioactive substances called nutraceuticals that come from whole foods including fruits, vegetables, herbs, and spices have drawn interest because of their ability to mitigate the negative effects of pesticide residues. These substances, which include minerals, vitamins, antioxidants, and polyphenols, have a variety of biological actions that may assist in the body's detoxification and healing of harm from pesticide exposure. In this context, this review aims to explore the potential of nutraceutical interventions as a promising strategy to mitigate the toxic effects of pesticide residues.
... Paraquat is an herbicide commonly used that has been linked to the occurrence of Parkinson's disease and other neurodegenerative diseases [164]. The compound is extremely harmful and induces oxidative stress by generating reactive oxygen species (ROS), resulting in neuronal damage and ultimately leading to neurodegeneration [165]. The mechanisms by which PQ induces neurodegeneration are complex and multifaceted. ...
Background
Neuroinflammation is a key pathological feature of a wide variety of neurological disorders, including Parkinson’s, multiple sclerosis, Alzheimer’s, and Huntington’s disease. While current treatments for these disorders are primarily symptomatic, there is a growing interest in developing new therapeutics that target the underlying neuroinflammatory processes.
Main body
Marine invertebrates, such as coral, sea urchins, starfish, sponges, and sea cucumbers, have been found to contain a wide variety of biologically active compounds that have demonstrated potential therapeutic properties. These compounds are known to target various key proteins and pathways in neuroinflammation, including 6-hydroxydopamine (OHDH), caspase-3 and caspase-9, p-Akt, p-ERK, p-P38, acetylcholinesterase (AChE), amyloid-β (Aβ), HSF-1, α-synuclein, cellular prion protein, advanced glycation end products (AGEs), paraquat (PQ), and mitochondria DJ-1.
Short conclusion
This review focuses on the current state of research on the neuroprotective effects of compounds found in marine invertebrates and the potential therapeutic implications of these findings for treating neuroinflammatory disorders. We also discussed the challenges and limitations of using marine-based compounds as therapeutics, such as sourcing and sustainability concerns, and the need for more preclinical and clinical studies to establish their efficacy and safety.
Graphical abstract
... Paraquat is considered as a substance inducing Parkinson's-like pathology in animals and therefore is also used for modeling this pathology in monoaminergic cell culture (such as neuroblastoma SH-SY5Y or pheochromacytoma PC-12 [55][56][57]). Monoamine metabolism is very sensitive to oxidative stress produced by paraquat through dopamine quinone production, affecting mitochondrial function and protein folding [58][59][60]. In our experiments, we adhered to a paraquat concentration of 800 µmol/L, stably resulting in 50% differentiated SH-SY5Y cell culture viability. ...
Phaeophyceae (brown algae) essentially contribute to biotopes of cold and temperate seas. Their thalli are rich in biologically active natural products, which are strongly and universally dominated with phlorotannins—polyphenols of complex and diverse structure based on multiple differently arranged phloroglucinol units and well known as strong antioxidants with a broad spectrum of biological activities. In the algal cells, phlorotannins can either accumulate in the cytoplasm or can be secreted into the cell wall (CW). The biological activities of extractable intracellular phlorotannins have been comprehensively characterized, whereas the properties of the CW-bound polyphenol fraction are still mostly unknown. Recently, we identified dibenzodioxin bonding as the principal structural feature of the CW-bound phlorotannins in fucoid algae, whereas soluble intracellular phlorotannins rely on aryl and ether bonds. However, profiles of biological activity associated with these structural differences are still unknown. Therefore, to the best of our knowledge, for the first time we address the antioxidant, cytotoxic, neuroprotective, and antibacterial properties of the CW-bound phlorotannin fractions isolated from two representatives of the order Fucales—Fucus vesiculosus and Pelvetia canaliculata. The CW-bound phlorotannins appeared to be softer antioxidants, stronger antibacterial agents and were featured with essentially less cytotoxicity in comparison to the intracellular fraction. However, the neuroprotective effects of both sub-cellular phlorotannin fractions of F. vesiculosus and P. canaliculata were similar. Thus, due to their lower cytotoxicity, CW-bound phlorotannins can be considered as promising antioxidants and neuroprotectors.
... Induction of oxidative stress is the most common mechanism and appears to be critical in NSCs undergoing toxic exposures (see Tables 1 and 2) [12,48,49,66,82]. Compelling evidence shows that MeHg-induced reactive oxygen species (ROS) formation and impaired mitochondrial function, as shown by in vivo and in vitro studies [83]. ...
Exposure to chemicals may pose a greater risk to vulnerable groups, including pregnant women, fetuses, and children, that may lead to diseases linked to the toxicants’ target organs. Among chemical contaminants, methylmercury (MeHg), present in aquatic food, is one of the most harmful to the developing nervous system depending on time and level of exposure. Moreover, certain man-made PFAS, such as PFOS and PFOA, used in commercial and industrial products including liquid repellants for paper, packaging, textile, leather, and carpets, are developmental neurotoxicants. There is vast knowledge about the detrimental neurotoxic effects induced by high levels of exposure to these chemicals. Less is known about the consequences that low-level exposures may have on neurodevelopment, although an increasing number of studies link neurotoxic chemical exposures to neurodevelopmental disorders. Still, the mechanisms of toxicity are not identified. Here we review in vitro mechanistic studies using neural stem cells (NSCs) from rodents and humans to dissect the cellular and molecular processes changed by exposure to environmentally relevant levels of MeHg or PFOS/PFOA. All studies show that even low concentrations dysregulate critical neurodevelopmental steps supporting the idea that neurotoxic chemicals may play a role in the onset of neurodevelopmental disorders.
... Oxidative stress may occur due to an increase in ROS production or the failure of their removal because of a decrease in ROS scavengers in the system [56]. Pesticides are a class of chemicals that have been shown in the past to affect this redox balance, thus oxidative stress is one of the often-reported toxicity mechanisms of pesticides [57,58]. ...
Earthworms are key organisms of the soil ecosystem and bioindicators for soil quality. While pesticides are used for the improvement of crop yields, they also present a burden for soil organisms. To understand the complex effects of pesticides on soil organisms, it is important to test these effects in soil exposures to include influences of the soil matrix on the toxicity. Therefore, the aim of this study was the assessment of the effects pesticides on earthworm Eisenia andrei. In an initial screening, active ingredients and commercial preparations were tested for comparison. Since the commercial preparations showed a higher toxicity, all further investigations (biomarkers, multixenobiotic resistance (MXR) activity, and avoidance behavior) were performed using the commercial pesticide formulations only: Sumialfa (esfenvalerate), Calypso (thiacloprid), Frontier (dimethenamid-p), and Filon (prosulfocarb). Significant differences in avoidance behavior were observed for Filon and Frontier. All pesticides inhibited the MXR activity and affected oxidative stress-related markers. Frontier was the only pesticide that did not affect enzymatic biomarkers related to neurotransmission. The results show the potential hazards associated with the usage of the tested pesticides and the importance of evaluating the effects of commercial pesticide preparations for a more realistic insight into the adverse effects on the environment.
... Paraquat is considered as a substance inducing Parkinson-like pathology in animals and therefore is also used for modeling this pathology in monoaminergic cell culture (such as neuroblastoma SH-SY5Y or pheochromacytoma PC-12, [55][56][57]. Monoamine metabolism is very sensitive to oxidative stress produced by paraquat through dopamine quinones production, affecting mitochondrial function and protein folding [58][59][60]. In our experiments we adhered to paraquat concentration 800 μmol/L, stably resulting in 50% differentiated SH-SY5Y cell culture viability. ...
The Phaeophyceae (brown algae) essentially contribute to biotopes of cold and temperate seas. Their thalli are rich in biologically active natural products which are strongly and universally dominated with phlorotannins – polyphenols of complex and diverse structure based on multiple differently arranged phloroglucinol units. These electron-rich compounds are strong antioxidants with antimicrobial, anti-inflammatory and neuroprotective activities. In the algal cells phlorotannins can either accumulate in cytoplasm or can be secreted into the cell wall (CW) with subsequent covalent binding to the alginate network. The biological activities of easily extractable intracellular phlorotannins were comprehensively characterized, whereas the properties of the CW-bound polyphenol fraction are still mostly unknown. Recently, we identified dibenzodioxin bonding as the principal structural feature of the CW-bound phlorotannins of fucoid algae, whereas soluble intracellular phlorotannins relied on aryl- and ether bonds. However, profiles of biological activity associated with these structural differences are still unknown. Therefore, here, to the best of our knowledge, for the first time, we address the antioxidant, cytotoxic, neuroprotective, and antibacterial properties of the CW-bound phlorotannin fractions isolated from two representatives of the order Fucales - Fucus vesiculosus and Pelvetia canaliculata. The CW-bound phlorotannins appeared to be softer antioxidants, stronger antibacterial agents and were featured with essentially less cytotoxicity in comparison to the intracellular fraction. However, the neuroprotective effects of both sub-cellular phlorotannin fractions of F. vesiculosus and P. canaliculata were essentially similar. Thus, due to their lower cytotoxicity, CW-bound phlorotannins can be considered as promising antioxidants and neuroprotectors.
... In agreement with previous studies, we have demonstrated that maneb induces oxidative stress in mouse brains. However, it has been reported that maneb does not exacerbate the toxicity of paraquat by increasing ROS in cells (Colle et al., 2018). In the present study, we observed a significant increase in ROS in SH-SY5Y cells exposed to 10 and 20 μM maneb. ...
Maneb, a widely-used dithiocarbamate fungicide, remains in the environment and exerts adverse health effects. Epidemiological evidence shows that maneb exposure is associated with a higher risk of Parkinson’s disease (PD), one of the most common neurodegenerative diseases. However, the molecular mechanisms underlying maneb-induced neurotoxicity remain unclear. Here we investigated the toxic effects and the underlying mechanisms of maneb on the degeneration of dopaminergic cells and α-synuclein in A53T transgenic mice. In SH-SY5Y cells, exposure to maneb reduces cell viability, triggers neuronal apoptosis, induces mitochondrial dysfunction, and generates reactive oxidative species (ROS) in a dose-dependent manner. Furthermore, Western blot analysis found that the mitochondrial apoptosis pathway (Bcl-2, Bax, cytochrome c, activated caspase-3) and the PKA/CREB signaling pathway (PKA, PDE10A, CREB, p-CREB) were changed by maneb both in vitro and in vivo. In addition, the activation of the mitochondrial apoptosis pathway induced by maneb was attenuated by activating PKA. Therefore, these results suggest that the PKA/CREB signaling pathway is involved in maneb-induced apoptosis. This study provides novel insights into maneb-induced neurotoxicity and the underlying mechanisms, which may serve as a guide for further toxicological assessment and standard application of maneb.
... Maneb treatment was reported to induce characteristics of PD in mice, including the degeneration of the nigrostriatal dopaminergic pathway (Ding et al., 2020;Hou et al., 2020). In vitro experiments also showed that exposure to maneb could induce neuronal cell death (Colle et al., 2018), mitochondrial dysfunction (Anderson et al., 2021), and oxidative stress (Hoffman et al., 2016;Anderson et al., 2018;Hoffman and Hardej, 2012). Additionally, maneb could induce the aggregation of α-synuclein in cells and mice, the hallmark of PD (Hou et al., 2019;Ishido, 2007). ...
... Paraquat and maneb are frequently used to explore the mechanisms of PD (Ding et al., 2020;Colle et al., 2018Colle et al., , 2020. Nevertheless, data concerning the molecular mechanisms of maneb-induced PD-like neurotoxicity are limited. ...
Maneb is a typical dithiocarbamate fungicide that has been extensively used worldwide. Epidemiological evidence shows that exposure to maneb is an environmental risk factor for Parkinson's disease (PD). However, the mechanisms underlying maneb-induced neurotoxicity have yet to be elucidated. In this study, we exposed SH-SY5Y cells to maneb at environmentally relevant concentrations (0, 0.1, 5, 10 mg/L) and found that maneb dose-dependently decreased the cell viability. Furthermore, maneb (60 mg/kg) induced PD-like motor impairment in α-synuclein A53T transgenic mice. The results of tandem mass tag (TMT) proteomics and metabolomics studies of mouse brain and serum revealed significant changes in proteins and metabolites in the pathways involved in the neurotransmitter system. The omics results were verified by targeted metabolomics and Western blot analysis, which demonstrated that maneb induced disturbance of the PD-related pathways, including the phenylalanine and tryptophan metabolism pathways, dopaminergic synapse, synaptic vesicle cycle, mitochondrial dysfunction, and oxidative stress. In addition, the PD-like phenotype induced by maneb was attenuated by the asparagine endopeptidase (AEP) inhibitor compound #11 (CP11) (10 mg/kg), indicating that AEP may play a role in maneb-induced neurotoxicity. To the best of our knowledge, this is the first study to investigate the molecular mechanisms underlying maneb-induced PD-like phenotypes using multiomics analysis, which identified novel therapeutic targets for PD associated with pesticides and other environmental pollutants.
... The organophosphates (OPs), organochlorines (OCs), carbamates, and pyrethroids are four classes of pesticides. These pesticides affect neurodegenerative and neurodevelopmental disorders such as ASD through various toxicological pathways [4,5]. Maternal exposure during the second and third trimesters of pregnancy to environmental pesticides can dramatically change cell division/proliferation, cell migration/differentiation, synaptic formation, and apoptosis; consequentely, it increases the ASD progression risk in children, even at low doses that are not harmful to the adult brain [5,6]. ...
... These pesticides affect neurodegenerative and neurodevelopmental disorders such as ASD through various toxicological pathways [4,5]. Maternal exposure during the second and third trimesters of pregnancy to environmental pesticides can dramatically change cell division/proliferation, cell migration/differentiation, synaptic formation, and apoptosis; consequentely, it increases the ASD progression risk in children, even at low doses that are not harmful to the adult brain [5,6]. Pesticides could be associated with some characteristics related to ASD by affecting brain development. ...
... There are some of evidence that neurodevelopmental toxicity is induced by the herbicide paraquat (PQ) and the fungicide maneb (MB) in vivo [5]. Early exposure to PQ + MB was reported to negatively affect embryonic neural stem cell (NSC) proliferation by targeting central cell cyclerelated factors (namely cyclin D1, cyclin D2, Rb1, and p19), and consequently, it leads to cell cycle arrest. ...
Autism spectrum disorder (ASD) increased dramatically over the past 25 years because of genetic and environmental factors. This systematic review (SR) aimed to determine the association between maternal exposure during pregnancy to environmental pesticides and other associations with the risk of ASD progression in children. PubMed (MEDLINE), Scopus (Elsevier) and the Institute for Scientific Information (ISI) Web of Science were searched using appropriate keywords up to March 2021. Twenty-four studies met the inclusion/exclusion criteria and were selected. Most studies reported that ASD increases the risk of offspring after prenatal exposure to environmental pesticides in pregnant mother’s residences, against offspring of women from the same region without this exposure. The main potential mechanisms inducing ASD progressions are ROS and prostaglandin E2 synthesis, AChE inhibition, voltage-gated sodium channel disruption, and GABA inhibition. According to the included studies, the highest rates of ASD diagnosis increased relative to organophosphates, and the application of the most common pesticides near residences might enhance the prevalence of ASD.
