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Tytuł:
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Co-exposure of melamine and cyanuric acid as a risk factor for oxidative stress and energy metabolism: Adverse effects on hippocampal neuronal and synaptic function induced by excessive ROS production.
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Autorzy:
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Sun W; Department of Pediatric, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Behavioral Neuroscience Laboratory, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China.
Chen X; Behavioral Neuroscience Laboratory, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Graduate School of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Mei Y; Graduate School of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Li X; Department of Neurology, Jinan Geriatric/Rehabilitation Hospital, Jinan 250013, China.
Yang Y; Department of Pediatric, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China.
An L; Department of Pediatric, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Behavioral Neuroscience Laboratory, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China; Department of Neurology, Jinan Geriatric/Rehabilitation Hospital, Jinan 250013, China; Department of Neurology, The First Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550001, China. Electronic address: al_.
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Źródło:
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Ecotoxicology and environmental safety [Ecotoxicol Environ Saf] 2022 Dec 01; Vol. 247, pp. 114230. Date of Electronic Publication: 2022 Oct 25.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Original Publication: Amsterdam, Netherlands : Elsevier
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MeSH Terms:
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CA1 Region, Hippocampal*/metabolism
Neurons*
Reactive Oxygen Species/metabolism ; Hippocampus ; Oxidative Stress ; Energy Metabolism ; Risk Factors
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Contributed Indexing:
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Keywords: Apoptosis; Hippocampal neurons; Melamine and cyanuric acid; Reactive oxygen species; Synaptic plasticity
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Substance Nomenclature:
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N3GP2YSD88 (melamine)
H497R4QKTZ (cyanuric acid)
0 (Reactive Oxygen Species)
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Entry Date(s):
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Date Created: 20221028 Date Completed: 20221122 Latest Revision: 20221122
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Update Code:
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20240105
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DOI:
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10.1016/j.ecoenv.2022.114230
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PMID:
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36306617
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Melamine (MEL) and cyanuric acid (CA) alone have relatively low toxicity, but together they may cause serious damage to multiple organs, including the central nervous system, however, the underlying mechanism is unknown. This study aimed to determine and compare the neurotoxic effects of MEL (20 μg/mL), CA (20 μg/mL) and their combination (10 μg/mL MEL and 10 μg/mL CA) on cultured hippocampal neurons. The cell viability, apoptosis, anti-oxidative and energy metabolic indices were detected following 24 h of incubations. The miniature excitatory postsynaptic currents (mEPSCs), miniature inhibitory postsynaptic currents (mIPSCs) and synaptic plasticity in the hippocampal CA1 neurons were recorded. Moreover, ROS scavenger NAC was co-infused to investigate the potential mechanism. We found the complex of MEL and CA but not their alone caused severe cell death and disturbed energy production through activation caspase-3-mediated apoptosis. Meanwhile, the combination significantly reduced the amplitude, decay time and frequency of mEPSCs but not mIPSCs, indicating the pre- and post-synaptic inhibitory actions on neuronal activity. Paired-pulsed ratio (PPR) and long-term potentiation (LTP) at the Schaffer collateral-CA1 synapses were critically depressed. However, the co-application of NAC could effectively mitigate the cellular apoptosis, energy metabolism dysfunction and the impairments in neuronal and synaptic function. Our findings provide the first evidence that the combination of MEL and CA can exert more prominently neurotoxic effects than their alone and certify that one of the potential mechanisms for neuronal and synaptic dysfunction is the ROS-mediated signaling pathway.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)