Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish

The genotoxicity, development toxicity, carcinogenicity, and acute or chronic toxic effects of glutaraldehyde (GA), particularly during occupational exposure through its use as a fixative, disinfectant, and preservative, are well-documented but its effects on neurotoxicity have not been investigated...

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Main Authors: Ha-Na Oh, Donggon Yoo, Seungmin Park, Sangwoo Lee, Woo-Keun Kim
Format: Article
Language:English
Published: Elsevier 2022-09-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S014765132200731X
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author Ha-Na Oh
Donggon Yoo
Seungmin Park
Sangwoo Lee
Woo-Keun Kim
author_facet Ha-Na Oh
Donggon Yoo
Seungmin Park
Sangwoo Lee
Woo-Keun Kim
author_sort Ha-Na Oh
collection DOAJ
description The genotoxicity, development toxicity, carcinogenicity, and acute or chronic toxic effects of glutaraldehyde (GA), particularly during occupational exposure through its use as a fixative, disinfectant, and preservative, are well-documented but its effects on neurotoxicity have not been investigated. We performed in vitro and in vivo studies to examine the developmental neurotoxicity (DNT) of GA. Neurite outgrowth was examined in an in vitro co-culture model consisting of SH-SY5Y human neuroblastoma cells and human astrocytes. Cell Counting Kit-8, lactate dehydrogenase assay, and high-content screening revealed that GA significantly inhibited neurite outgrowth at non-cytotoxic concentration. Further studies showed that GA upregulated the mRNA expression of the astrocyte markers GFAP and S100β and downregulated the expression of the neurodevelopmental genes Nestin, βIII-tubulin, GAP43, and MAP2. Furthermore, in vivo zebrafish embryo toxicity tests explored the effects of GA on neural morphogenesis. GA adversely affected the early development of zebrafish embryos, resulting in decreased survival, irregular hatching, and reduced heart rate in a time- and concentration-dependent manner. Furthermore, the width of the brain and spinal cord was reduced, and the myelination of Schwann cells and oligodendrocytes was decreased by GA in transgenic zebrafish lines. These data suggest that GAs have potential DNT in vitro and in vivo, highlighting the need for caution regarding the neurotoxicity of GA.
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spelling doaj.art-4bf6b3eb1f7640c2bc9ced48e6476dcf2022-12-22T04:01:05ZengElsevierEcotoxicology and Environmental Safety0147-65132022-09-01242113891Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafishHa-Na Oh0Donggon Yoo1Seungmin Park2Sangwoo Lee3Woo-Keun Kim4Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, Republic of KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, Republic of KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of KoreaDepartment of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea; Human and Environmental Toxicology, University of Science and Technology, Daejeon 34113, Republic of Korea; Corresponding author at: Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea.The genotoxicity, development toxicity, carcinogenicity, and acute or chronic toxic effects of glutaraldehyde (GA), particularly during occupational exposure through its use as a fixative, disinfectant, and preservative, are well-documented but its effects on neurotoxicity have not been investigated. We performed in vitro and in vivo studies to examine the developmental neurotoxicity (DNT) of GA. Neurite outgrowth was examined in an in vitro co-culture model consisting of SH-SY5Y human neuroblastoma cells and human astrocytes. Cell Counting Kit-8, lactate dehydrogenase assay, and high-content screening revealed that GA significantly inhibited neurite outgrowth at non-cytotoxic concentration. Further studies showed that GA upregulated the mRNA expression of the astrocyte markers GFAP and S100β and downregulated the expression of the neurodevelopmental genes Nestin, βIII-tubulin, GAP43, and MAP2. Furthermore, in vivo zebrafish embryo toxicity tests explored the effects of GA on neural morphogenesis. GA adversely affected the early development of zebrafish embryos, resulting in decreased survival, irregular hatching, and reduced heart rate in a time- and concentration-dependent manner. Furthermore, the width of the brain and spinal cord was reduced, and the myelination of Schwann cells and oligodendrocytes was decreased by GA in transgenic zebrafish lines. These data suggest that GAs have potential DNT in vitro and in vivo, highlighting the need for caution regarding the neurotoxicity of GA.http://www.sciencedirect.com/science/article/pii/S014765132200731XGlutaraldehydeDevelopmental neurotoxicityCo-cultureZebrafish
spellingShingle Ha-Na Oh
Donggon Yoo
Seungmin Park
Sangwoo Lee
Woo-Keun Kim
Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish
Ecotoxicology and Environmental Safety
Glutaraldehyde
Developmental neurotoxicity
Co-culture
Zebrafish
title Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish
title_full Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish
title_fullStr Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish
title_full_unstemmed Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish
title_short Developmental neurotoxicity induced by glutaraldehyde in neuron/astrocyte co-cultured cells and zebrafish
title_sort developmental neurotoxicity induced by glutaraldehyde in neuron astrocyte co cultured cells and zebrafish
topic Glutaraldehyde
Developmental neurotoxicity
Co-culture
Zebrafish
url http://www.sciencedirect.com/science/article/pii/S014765132200731X
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