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      Biomonitoring of blood cholinesterases and acylpeptide hydrolase activities in rural inhabitants exposed to pesticides in the Coquimbo Region of Chile

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          Abstract

          In Chile, agriculture is a relevant economic activity and is concomitant with the use of pesticides to improve the yields. Acute intoxications of agricultural workers occur with some frequency and they must be reported to the surveillance system of the Ministry of Health. However the impacts of chronic and environmental pesticide exposure have been less studied. Among pesticides frequently used in Chile for insects control are organophosphates (OP) and carbamates (CB). They are inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). In this study we determined the pattern of both biomarkers activity in three populations with different type of chronic exposure to OP/CB: environmentally exposed (EE), occupationally exposed (OE) and a reference group (RG) without exposure. Besides this, we also measured the activity of acylpeptide hydrolase (APEH), an enzyme involved in relevant functions in the central synapses that is also expressed in erythrocytes and previously reported to be highly inhibited by some OP. A baseline measurement was done in both exposure groups and then a second measurement was done during the spraying season. The RG was measured only once at any time of the year. Our results indicate that people under chronic OP/CB exposure showed an adaptive response through an increase of basal BChE activity. During the spray season only BChE activity was decreased in the EE and OE groups ( p<0.05 and p<0.01, respectively) and the higher magnitude of BChE inhibition was observed in the EE group. The analysis of the frequencies of inhibition above 30% (biological tolerance limit declared by Chilean legislation) indicated that BChE was most frequently inhibited in the EE group (53% of the individuals displayed inhibition) and AChE in the OE group (55% of the individuals displayed AChE inhibition). APEH activity showed the highest frequency of inhibition in the EE group independent of its magnitude (64%). Our results demonstrate that the rural population living nearby agricultural settings displays high levels of environmental exposure. APEH activity seems to be a sensitive biomarker for acute low-level exposure and its usefulness as a routine biomarker must to be explored in future studies. Systematic biomonitoring and health outcomes studies are necessary as well as obtaining the baseline for BChE and AChE activity levels with the aim to improve environmental and occupational health policies in Chile.

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          Association of Pesticide Exposure with Neurologic Dysfunction and Disease

          Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neuro-toxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease.
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            Current issues in organophosphate toxicology.

            Organophosphates (OPs) are one of the main classes of insecticides, in use since the mid 1940s. OPs can exert significant adverse effects in non-target species including humans. Because of the phosphorylation of acetylcholinesterase, they exert primarily a cholinergic toxicity, however, some can also cause a delayed polyneuropathy. Currently debated and investigated issues in the toxicology of OPs are presented in this review. These include: 1) possible long-term effects of chronic low-level exposures; 2) genetic susceptibility to OP toxicity; 3) developmental toxicity and neurotoxicity; 4) common mechanism of action; 5) mechanisms of delayed neurotoxicity; and 6) possible additional OP targets. Continuing and recent debates, and molecular advances in these areas, and their contributions to our understanding of the toxicology of OPs are discussed.
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              Acetylcholinesterase as a Biomarker in Environmental and Occupational Medicine: New Insights and Future Perspectives

              Acetylcholinesterase (AChE) is a key enzyme in the nervous system. It terminates nerve impulses by catalysing the hydrolysis of neurotransmitter acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, acetylcholinesterase activity and its inhibition has been early recognized to be a human biological marker of pesticide poisoning. Measurement of AChE inhibition has been increasingly used in the last two decades as a biomarker of effect on nervous system following exposure to organophosphate and carbamate pesticides in occupational and environmental medicine. The success of this biomarker arises from the fact that it meets a number of characteristics necessary for the successful application of a biological response as biomarker in human biomonitoring: the response is easy to measure, it shows a dose-dependent behavior to pollutant exposure, it is sensitive, and it exhibits a link to health adverse effects. The aim of this work is to review and discuss the recent findings about acetylcholinesterase, including its sensitivity to other pollutants and the expression of different splice variants. These insights open new perspective for the future use of this biomarker in environmental and occupational human health monitoring.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Methodology
                Role: Formal analysisRole: Investigation
                Role: Formal analysis
                Role: Supervision
                Role: Supervision
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 May 2018
                2018
                : 13
                : 5
                : e0196084
                Affiliations
                [1 ] Department of Public Health, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile
                [2 ] Department of Primary and Community Care, Radboud university medical center, Nijmegen, The Netherlands
                [3 ] Laboratory of Environmental Neurotoxicology, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile
                [4 ] Laboratory of Biomedical Research, Faculty of Medicine, Universidad Católica del Maule, Talca, Chile
                [5 ] Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands
                Weizmann Institute of Science, ISRAEL
                Author notes

                Competing Interests: The authors have declared that no competng interests exist.

                Author information
                http://orcid.org/0000-0002-6990-9832
                Article
                PONE-D-18-01652
                10.1371/journal.pone.0196084
                5931667
                29718943
                e1dd3789-c77a-458f-8324-ac55b2a94769
                © 2018 Ramírez-Santana et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 16 January 2018
                : 5 April 2018
                Page count
                Figures: 4, Tables: 4, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100008736, Fondo de Fomento al Desarrollo Científico y Tecnológico;
                Award ID: D09I1057
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002850, Fondo Nacional de Desarrollo Científico y Tecnológico;
                Award ID: 3120231
                Award Recipient :
                This work was supported by the Fondo de Fomento al Desarrollo Científico y Tecnológico D09I1057 (MRS, RS and FP; www.conicyt.cl/fondef/) and Fondo Nacional de Desarrollo Científico y Tecnológico 3120231 (LZV; www.conicyt.cl/fondecyt/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Agriculture
                Agrochemicals
                Pesticides
                Biology and Life Sciences
                Agriculture
                Pest Control
                Pesticides
                Biology and Life Sciences
                Biochemistry
                Biomarkers
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Blood Cells
                Red Blood Cells
                People and places
                Geographical locations
                South America
                Chile (Country)
                Biology and Life Sciences
                Biochemistry
                Enzymology
                Enzyme Inhibitors
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Blood Plasma
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Physiology
                Body Fluids
                Blood
                Blood Plasma
                Medicine and Health Sciences
                Public and Occupational Health
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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