Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice

Detalhes bibliográficos
Autor(a) principal: da Luz, Thiarlen Marinho
Data de Publicação: 2022
Outros Autores: Araújo, Amanda Pereira da Costa, Rezende, Fernanda Neves Estrêla, Silva, Abner Marcelino, Charlie-Silva, Ives, Braz, Helyson Lucas Bezerra, Sanches, Paulo R.S. [UNESP], Rahman, Md. Mostafizur, Barceló, Damià, Malafaia, Guilherme
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.neuro.2022.03.012
http://hdl.handle.net/11449/223782
Resumo: Despite advances in research on the vaccine and therapeutic strategies of COVID-19, little attention has been paid to the possible (eco)toxicological impacts of the dispersion of SARS-CoV-2 particles in natural environments. Thus, in this study, we aimed to evaluate the behavioral and biochemical consequences of the short exposure of outbred and inbred mice (male Swiss and C57Bl/6 J mice, respectively) to PSPD-2002 (peptide fragments of the Spike protein of SARS-CoV-2) synthesized in the laboratory. Our data demonstrated that after 24 h of intraperitoneal administration of PSPD-2002 (at 580 μg/kg) the animals did not present alterations in their locomotor, anxiolytic-like, or anxiety-like behavior (in the open field test), nor antidepressant-like or depressive behavior in the forced swimming test. However, the C57Bl/6 J mice exposed to PSPD-2002 showed memory deficit in the novel object recognition task, which was associated with higher production of thiobarbituric acid reactive substances, as well as the increased suppression of acetylcholinesterase brain activity, compared to Swiss mice also exposed to peptide fragments. In Swiss mice the reduction in the activity of superoxide dismutase and catalase in the brain was not associated with increased oxidative stress biomarkers (hydrogen peroxide), suggesting that other antioxidant mechanisms may have been activated by exposure to PSPD-2002 to maintain the animals' brain redox homeostasis. Finally, the results of all biomarkers evaluated were applied into the “Integrated Biomarker Response Index” (IBRv2) and the principal component analysis (PCA), and greater sensitivity of C57Bl/6 J mice to PSPD-2002 was revealed. Therefore, our study provides pioneering evidence of mammalian exposure-induced toxicity (non-target SARS-CoV-2 infection) to PSPD-2002, as well as “sheds light” on the influence of genetic profile on susceptibility/resistance to the effects of viral peptide fragments.
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spelling Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred miceC57Bl/6 J miceEnvironmental ToxicologyPandemic COVID-19ProteinsSwiss miceDespite advances in research on the vaccine and therapeutic strategies of COVID-19, little attention has been paid to the possible (eco)toxicological impacts of the dispersion of SARS-CoV-2 particles in natural environments. Thus, in this study, we aimed to evaluate the behavioral and biochemical consequences of the short exposure of outbred and inbred mice (male Swiss and C57Bl/6 J mice, respectively) to PSPD-2002 (peptide fragments of the Spike protein of SARS-CoV-2) synthesized in the laboratory. Our data demonstrated that after 24 h of intraperitoneal administration of PSPD-2002 (at 580 μg/kg) the animals did not present alterations in their locomotor, anxiolytic-like, or anxiety-like behavior (in the open field test), nor antidepressant-like or depressive behavior in the forced swimming test. However, the C57Bl/6 J mice exposed to PSPD-2002 showed memory deficit in the novel object recognition task, which was associated with higher production of thiobarbituric acid reactive substances, as well as the increased suppression of acetylcholinesterase brain activity, compared to Swiss mice also exposed to peptide fragments. In Swiss mice the reduction in the activity of superoxide dismutase and catalase in the brain was not associated with increased oxidative stress biomarkers (hydrogen peroxide), suggesting that other antioxidant mechanisms may have been activated by exposure to PSPD-2002 to maintain the animals' brain redox homeostasis. Finally, the results of all biomarkers evaluated were applied into the “Integrated Biomarker Response Index” (IBRv2) and the principal component analysis (PCA), and greater sensitivity of C57Bl/6 J mice to PSPD-2002 was revealed. Therefore, our study provides pioneering evidence of mammalian exposure-induced toxicity (non-target SARS-CoV-2 infection) to PSPD-2002, as well as “sheds light” on the influence of genetic profile on susceptibility/resistance to the effects of viral peptide fragments.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Biological Research Laboratory Goiano Federal Institute, GOPost-Graduation Program in Environmental Sciences Federal University of Goiás, GODepartment of Pharmacology Institute of Biomedical Sciences University of São Paulo, SPDrug Research and Development Center Federal University of Ceará, CEInstitute of Chemistry São Paulo State University, SPLaboratory of Environmental Health and Ecotoxicology Department of Environmental Sciences Jahangirnagar UniversityCatalan Institute for Water Research (ICRA-CERCA) H2O Building Scientific and Technological Park of the University of Girona, Emili Grahit 101Water and Soil Quality Research Group Department of Environmental Chemistry Institute of Environmental Assessment and Water Research (IDAEA-CSIC), JordiGirona 1826Post-Graduation Program in Conservation of Cerrado Natural Resources Goiano Federal Institute, GOPost-Graduation Program in Ecology Conservation and Biodiversity Federal University of Uberlândia, MGPost-Graduation Programa in Biotechnology and Biodiversity Federal University of Goiás, GOInstitute of Chemistry São Paulo State University, SPCNPq: 23219.000137.2022-28CNPq: 307743/2018-7CNPq: 403065/2021-6Goiano Federal InstituteUniversidade Federal de Goiás (UFG)Universidade de São Paulo (USP)Federal University of CearáUniversidade Estadual Paulista (UNESP)Jahangirnagar UniversityScientific and Technological Park of the University of GironaInstitute of Environmental Assessment and Water Research (IDAEA-CSIC)Universidade Federal de Uberlândia (UFU)da Luz, Thiarlen MarinhoAraújo, Amanda Pereira da CostaRezende, Fernanda Neves EstrêlaSilva, Abner MarcelinoCharlie-Silva, IvesBraz, Helyson Lucas BezerraSanches, Paulo R.S. [UNESP]Rahman, Md. MostafizurBarceló, DamiàMalafaia, Guilherme2022-04-28T19:52:59Z2022-04-28T19:52:59Z2022-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article184-196http://dx.doi.org/10.1016/j.neuro.2022.03.012NeuroToxicology, v. 90, p. 184-196.1872-97110161-813Xhttp://hdl.handle.net/11449/22378210.1016/j.neuro.2022.03.0122-s2.0-85127765187Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengNeuroToxicologyinfo:eu-repo/semantics/openAccess2022-04-28T19:52:59Zoai:repositorio.unesp.br:11449/223782Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T22:14:21.924098Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
title Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
spellingShingle Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
da Luz, Thiarlen Marinho
C57Bl/6 J mice
Environmental Toxicology
Pandemic COVID-19
Proteins
Swiss mice
title_short Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
title_full Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
title_fullStr Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
title_full_unstemmed Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
title_sort Shedding light on the toxicity of SARS-CoV-2-derived peptide in non-target COVID-19 organisms: A study involving inbred and outbred mice
author da Luz, Thiarlen Marinho
author_facet da Luz, Thiarlen Marinho
Araújo, Amanda Pereira da Costa
Rezende, Fernanda Neves Estrêla
Silva, Abner Marcelino
Charlie-Silva, Ives
Braz, Helyson Lucas Bezerra
Sanches, Paulo R.S. [UNESP]
Rahman, Md. Mostafizur
Barceló, Damià
Malafaia, Guilherme
author_role author
author2 Araújo, Amanda Pereira da Costa
Rezende, Fernanda Neves Estrêla
Silva, Abner Marcelino
Charlie-Silva, Ives
Braz, Helyson Lucas Bezerra
Sanches, Paulo R.S. [UNESP]
Rahman, Md. Mostafizur
Barceló, Damià
Malafaia, Guilherme
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Goiano Federal Institute
Universidade Federal de Goiás (UFG)
Universidade de São Paulo (USP)
Federal University of Ceará
Universidade Estadual Paulista (UNESP)
Jahangirnagar University
Scientific and Technological Park of the University of Girona
Institute of Environmental Assessment and Water Research (IDAEA-CSIC)
Universidade Federal de Uberlândia (UFU)
dc.contributor.author.fl_str_mv da Luz, Thiarlen Marinho
Araújo, Amanda Pereira da Costa
Rezende, Fernanda Neves Estrêla
Silva, Abner Marcelino
Charlie-Silva, Ives
Braz, Helyson Lucas Bezerra
Sanches, Paulo R.S. [UNESP]
Rahman, Md. Mostafizur
Barceló, Damià
Malafaia, Guilherme
dc.subject.por.fl_str_mv C57Bl/6 J mice
Environmental Toxicology
Pandemic COVID-19
Proteins
Swiss mice
topic C57Bl/6 J mice
Environmental Toxicology
Pandemic COVID-19
Proteins
Swiss mice
description Despite advances in research on the vaccine and therapeutic strategies of COVID-19, little attention has been paid to the possible (eco)toxicological impacts of the dispersion of SARS-CoV-2 particles in natural environments. Thus, in this study, we aimed to evaluate the behavioral and biochemical consequences of the short exposure of outbred and inbred mice (male Swiss and C57Bl/6 J mice, respectively) to PSPD-2002 (peptide fragments of the Spike protein of SARS-CoV-2) synthesized in the laboratory. Our data demonstrated that after 24 h of intraperitoneal administration of PSPD-2002 (at 580 μg/kg) the animals did not present alterations in their locomotor, anxiolytic-like, or anxiety-like behavior (in the open field test), nor antidepressant-like or depressive behavior in the forced swimming test. However, the C57Bl/6 J mice exposed to PSPD-2002 showed memory deficit in the novel object recognition task, which was associated with higher production of thiobarbituric acid reactive substances, as well as the increased suppression of acetylcholinesterase brain activity, compared to Swiss mice also exposed to peptide fragments. In Swiss mice the reduction in the activity of superoxide dismutase and catalase in the brain was not associated with increased oxidative stress biomarkers (hydrogen peroxide), suggesting that other antioxidant mechanisms may have been activated by exposure to PSPD-2002 to maintain the animals' brain redox homeostasis. Finally, the results of all biomarkers evaluated were applied into the “Integrated Biomarker Response Index” (IBRv2) and the principal component analysis (PCA), and greater sensitivity of C57Bl/6 J mice to PSPD-2002 was revealed. Therefore, our study provides pioneering evidence of mammalian exposure-induced toxicity (non-target SARS-CoV-2 infection) to PSPD-2002, as well as “sheds light” on the influence of genetic profile on susceptibility/resistance to the effects of viral peptide fragments.
publishDate 2022
dc.date.none.fl_str_mv 2022-04-28T19:52:59Z
2022-04-28T19:52:59Z
2022-05-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.neuro.2022.03.012
NeuroToxicology, v. 90, p. 184-196.
1872-9711
0161-813X
http://hdl.handle.net/11449/223782
10.1016/j.neuro.2022.03.012
2-s2.0-85127765187
url http://dx.doi.org/10.1016/j.neuro.2022.03.012
http://hdl.handle.net/11449/223782
identifier_str_mv NeuroToxicology, v. 90, p. 184-196.
1872-9711
0161-813X
10.1016/j.neuro.2022.03.012
2-s2.0-85127765187
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv NeuroToxicology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 184-196
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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