The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation

Cypermethrin (CMN) is a widely used artificial synthetic pesticide that causes neurotoxicity in the hippocampus. However, the underlying toxicological targets and mechanisms remain unclear. In this study, network pharmacology analysis and in vitro models were integrated to investigate the effect and...

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Autores principales:	Jianan Li, Haoran Bi
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	network pharmacology experimental validation cypermethrin hippocampal neurotoxicity Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/85d8792260f94c6b8760b1fccbc1867b
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spelling	oai:doaj.org-article:85d8792260f94c6b8760b1fccbc1867b2021-11-26T11:19:49ZThe effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation2165-59792165-598710.1080/21655979.2021.2000106https://doaj.org/article/85d8792260f94c6b8760b1fccbc1867b2021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.2000106https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Cypermethrin (CMN) is a widely used artificial synthetic pesticide that causes neurotoxicity in the hippocampus. However, the underlying toxicological targets and mechanisms remain unclear. In this study, network pharmacology analysis and in vitro models were integrated to investigate the effect and mechanism of CMN-induced hippocampal neurotoxicity. A total of 88 targets of CMN-induced hippocampal neurotoxicity were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analyses suggested that these targets were related to multiple GO terms and signaling pathways. To further investigate underlying mechanism, the top 10 hub targets (Akt1, Tnf, Ptgs2, Casp3, Igf1, Sirt1, Jun, Cat, Il10, and Bcl2l1) were screened. Furthermore, cell viability and lactate dehydrogenase (LDH) assays demonstrated that CMN was toxic to HT22 cells in a time- and dose-dependent manner. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining revealed that treatment with CMN increased the proportion of apoptotic cells. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) results indicated that CMN altered the mRNA expression levels of most of the hub targets, with the exceptions of Igf1 and Jun. The results demonstrated that multiple targets and signaling pathways were involved in CMN-induced hippocampal neurotoxicity. These findings provided reference values for subsequent studies of the toxicological mechanism of CMN.Jianan LiHaoran BiTaylor & Francis Grouparticlenetwork pharmacologyexperimental validationcypermethrinhippocampal neurotoxicityBiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 9279-9289 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	network pharmacology experimental validation cypermethrin hippocampal neurotoxicity Biotechnology TP248.13-248.65
spellingShingle	network pharmacology experimental validation cypermethrin hippocampal neurotoxicity Biotechnology TP248.13-248.65 Jianan Li Haoran Bi The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation
description	Cypermethrin (CMN) is a widely used artificial synthetic pesticide that causes neurotoxicity in the hippocampus. However, the underlying toxicological targets and mechanisms remain unclear. In this study, network pharmacology analysis and in vitro models were integrated to investigate the effect and mechanism of CMN-induced hippocampal neurotoxicity. A total of 88 targets of CMN-induced hippocampal neurotoxicity were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) analyses suggested that these targets were related to multiple GO terms and signaling pathways. To further investigate underlying mechanism, the top 10 hub targets (Akt1, Tnf, Ptgs2, Casp3, Igf1, Sirt1, Jun, Cat, Il10, and Bcl2l1) were screened. Furthermore, cell viability and lactate dehydrogenase (LDH) assays demonstrated that CMN was toxic to HT22 cells in a time- and dose-dependent manner. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining revealed that treatment with CMN increased the proportion of apoptotic cells. In addition, the real-time quantitative polymerase chain reaction (RT-qPCR) results indicated that CMN altered the mRNA expression levels of most of the hub targets, with the exceptions of Igf1 and Jun. The results demonstrated that multiple targets and signaling pathways were involved in CMN-induced hippocampal neurotoxicity. These findings provided reference values for subsequent studies of the toxicological mechanism of CMN.
format	article
author	Jianan Li Haoran Bi
author_facet	Jianan Li Haoran Bi
author_sort	Jianan Li
title	The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation
title_short	The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation
title_full	The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation
title_fullStr	The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation
title_full_unstemmed	The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation
title_sort	effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/85d8792260f94c6b8760b1fccbc1867b
work_keys_str_mv	AT jiananli theeffectandmechanismofcypermethrininducedhippocampalneurotoxicityasdeterminedbynetworkpharmacologyanalysisandexperimentalvalidation AT haoranbi theeffectandmechanismofcypermethrininducedhippocampalneurotoxicityasdeterminedbynetworkpharmacologyanalysisandexperimentalvalidation AT jiananli effectandmechanismofcypermethrininducedhippocampalneurotoxicityasdeterminedbynetworkpharmacologyanalysisandexperimentalvalidation AT haoranbi effectandmechanismofcypermethrininducedhippocampalneurotoxicityasdeterminedbynetworkpharmacologyanalysisandexperimentalvalidation
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The effect and mechanism of cypermethrin-induced hippocampal neurotoxicity as determined by network pharmacology analysis and experimental validation

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