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Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest

Aflatoxin B1 (AFB(1)) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damage...

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Autores principales: Huang, Boyan, Chen, Qingmei, Wang, Lingling, Gao, Xiaojuan, Zhu, Wenya, Mu, Peiqiang, Deng, Yiqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554769/
https://www.ncbi.nlm.nih.gov/pubmed/32899983
http://dx.doi.org/10.3390/ijms21186517
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author Huang, Boyan
Chen, Qingmei
Wang, Lingling
Gao, Xiaojuan
Zhu, Wenya
Mu, Peiqiang
Deng, Yiqun
author_facet Huang, Boyan
Chen, Qingmei
Wang, Lingling
Gao, Xiaojuan
Zhu, Wenya
Mu, Peiqiang
Deng, Yiqun
author_sort Huang, Boyan
collection PubMed
description Aflatoxin B1 (AFB(1)) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB(1) (300 μg/kg/day for 30 days). The toxicity of AFB(1) on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB(1) on IMR-32 cells were 6.18 μg/mL and 5.87 μg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB(1) concentration-dependent manner, which was associated with the upregulation of NOX2, and downregulation of OXR1, SOD1, and SOD2. Substantial DNA damage associated with the downregulation of PARP1, BRCA2, and RAD51 was also observed. Furthermore, AFB(1) significantly induced S-phase arrest, which is associated with the upregulation of CDKN1A, CDKN2C, and CDKN2D. Finally, AFB(1) induced apoptosis involving CASP3 and BAX. Taken together, AFB(1) manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis—all of which are key factors for understanding the neurotoxicology of AFB(1).
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spelling pubmed-75547692020-10-14 Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest Huang, Boyan Chen, Qingmei Wang, Lingling Gao, Xiaojuan Zhu, Wenya Mu, Peiqiang Deng, Yiqun Int J Mol Sci Article Aflatoxin B1 (AFB(1)) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB(1) (300 μg/kg/day for 30 days). The toxicity of AFB(1) on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB(1) on IMR-32 cells were 6.18 μg/mL and 5.87 μg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB(1) concentration-dependent manner, which was associated with the upregulation of NOX2, and downregulation of OXR1, SOD1, and SOD2. Substantial DNA damage associated with the downregulation of PARP1, BRCA2, and RAD51 was also observed. Furthermore, AFB(1) significantly induced S-phase arrest, which is associated with the upregulation of CDKN1A, CDKN2C, and CDKN2D. Finally, AFB(1) induced apoptosis involving CASP3 and BAX. Taken together, AFB(1) manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis—all of which are key factors for understanding the neurotoxicology of AFB(1). MDPI 2020-09-06 /pmc/articles/PMC7554769/ /pubmed/32899983 http://dx.doi.org/10.3390/ijms21186517 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Boyan
Chen, Qingmei
Wang, Lingling
Gao, Xiaojuan
Zhu, Wenya
Mu, Peiqiang
Deng, Yiqun
Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
title Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
title_full Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
title_fullStr Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
title_full_unstemmed Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
title_short Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest
title_sort aflatoxin b1 induces neurotoxicity through reactive oxygen species generation, dna damage, apoptosis, and s-phase cell cycle arrest
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554769/
https://www.ncbi.nlm.nih.gov/pubmed/32899983
http://dx.doi.org/10.3390/ijms21186517
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