Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress

Detalhes bibliográficos
Autor(a) principal: Eiró, Luciana Guimarães
Data de Publicação: 2020
Outros Autores: Ferreira, Maria Karolina Martins, Bittencourt, Leonardo Oliveira, Aragão, Walessa Alana Bragança, Souza, Michel Platini Caldas de, Silva, Marcia Cristina Freitas, Dionizio, Aline, Buzalaf, Marília Afonso Rabelo, Crespo-López, Maria Elena, Lima, Rafael Rodrigues
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
Texto Completo: https://patua.iec.gov.br/handle/iec/4186
Resumo: Methylmercury (MeHg) is considered by the World Health Organization (WHO) as one of the chemicals of greatest public health concern. Although central nervous system (CNS) is the main target organ, the effects over the spinal cord are not well understood, especially in chronic exposure at similar doses to those faced by humans. This study aimed to investigate possible changes on global proteomic profile and oxidative biochemistry status of rats spinal cord, related to the maintenance and balance of the organism functioning, mimicking a human daily exposure by diet (chronic and with relatively low levels). For this, 28 adults male Wistar rats were divided into two groups: MeHg group, which was intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg/kg/day for 60 days, and control group, that received only vehicle. After the exposure period, the spinal cords were collected for evaluation of total mercury levels, proteomic profile, with further bioinformatic overrepresentation analysis (ORA), and oxidative biochemistry, by analyzing the antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), nitrite levels, measurement of Trolox Equivalent Antioxidant Capacity (TEAC) and Reduced Glutathione (GSH). The MeHg exposure increased total mercury levels in spinal cord parenchyma, which increased lipid peroxidation and nitrite levels, and reduced antioxidant status. The proteomic analysis showed several proteins related to biological processes, cellular components and molecular functions. Moreover, according to the ORA analysis, the proteins are involved in processes such as mitochondrial activity, stress response, cytoskeleton and apoptosis. Therefore, we concluded that exposure to low doses of MeHg can activate the oxidative stress pathway and thus, modulate the status of regulation of several important proteins.
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spelling Eiró, Luciana GuimarãesFerreira, Maria Karolina MartinsBittencourt, Leonardo OliveiraAragão, Walessa Alana BragançaSouza, Michel Platini Caldas deSilva, Marcia Cristina FreitasDionizio, AlineBuzalaf, Marília Afonso RabeloCrespo-López, Maria ElenaLima, Rafael Rodrigues2020-10-19T14:02:00Z2020-10-19T14:02:00Z2020EIRÓ, Luciana Guimarães et al. Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress. Food and Chemical Toxicology, v. 146, n. 111772, Dec. 2020.0278-6915https://patua.iec.gov.br/handle/iec/418610.1016/j.fct.2020.111772Methylmercury (MeHg) is considered by the World Health Organization (WHO) as one of the chemicals of greatest public health concern. Although central nervous system (CNS) is the main target organ, the effects over the spinal cord are not well understood, especially in chronic exposure at similar doses to those faced by humans. This study aimed to investigate possible changes on global proteomic profile and oxidative biochemistry status of rats spinal cord, related to the maintenance and balance of the organism functioning, mimicking a human daily exposure by diet (chronic and with relatively low levels). For this, 28 adults male Wistar rats were divided into two groups: MeHg group, which was intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg/kg/day for 60 days, and control group, that received only vehicle. After the exposure period, the spinal cords were collected for evaluation of total mercury levels, proteomic profile, with further bioinformatic overrepresentation analysis (ORA), and oxidative biochemistry, by analyzing the antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), nitrite levels, measurement of Trolox Equivalent Antioxidant Capacity (TEAC) and Reduced Glutathione (GSH). The MeHg exposure increased total mercury levels in spinal cord parenchyma, which increased lipid peroxidation and nitrite levels, and reduced antioxidant status. The proteomic analysis showed several proteins related to biological processes, cellular components and molecular functions. Moreover, according to the ORA analysis, the proteins are involved in processes such as mitochondrial activity, stress response, cytoskeleton and apoptosis. Therefore, we concluded that exposure to low doses of MeHg can activate the oxidative stress pathway and thus, modulate the status of regulation of several important proteins.Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brasil (CNPq) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Brasil (CAPES) - Finance Code 001; Universidade Federal do Pará (PROPESP, UFPA, Brazil)Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.University of São Paulo. Department of Biological Sciences. Bauru Dental School. Bauru, SP, Brazil.University of São Paulo. Department of Biological Sciences. Bauru Dental School. Bauru, SP, Brazil.Federal University of Pará. Laboratory of Molecular Pharmacology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.engElsevierChronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stressinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSistema Nervoso CentralIntoxicação do Sistema Nervoso por MercúrioMercúrio / toxicidadeMedula EspinalEstresse OxidativoProteômicainfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALChronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress.pdfChronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress.pdfapplication/pdf551083https://patua.iec.gov.br/bitstreams/62732214-282e-4fad-8111-d924164bf11a/downloadc9a9c128e29cac82a5d7fdf3f4e6da73MD51TEXTChronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress.pdf.txtChronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress.pdf.txtExtracted texttext/plain2https://patua.iec.gov.br/bitstreams/925ecad2-7004-4329-8d19-09e2cb89740a/downloade1c06d85ae7b8b032bef47e42e4c08f9MD55THUMBNAILChronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress.pdf.jpgChronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress.pdf.jpgGenerated Thumbnailimage/jpeg3095https://patua.iec.gov.br/bitstreams/a21ffc21-1e59-49df-8399-16af5d6498ca/download71859d578212107f7f8c49a4ce09d9eeMD56LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/252df7b7-7a92-47f9-8efe-628820abe773/download11832eea31b16df8613079d742d61793MD52iec/41862022-10-20 21:47:50.914oai:patua.iec.gov.br:iec/4186https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-20T21:47:50Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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
dc.title.pt_BR.fl_str_mv Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
title Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
spellingShingle Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
Eiró, Luciana Guimarães
Sistema Nervoso Central
Intoxicação do Sistema Nervoso por Mercúrio
Mercúrio / toxicidade
Medula Espinal
Estresse Oxidativo
Proteômica
title_short Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
title_full Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
title_fullStr Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
title_full_unstemmed Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
title_sort Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress
author Eiró, Luciana Guimarães
author_facet Eiró, Luciana Guimarães
Ferreira, Maria Karolina Martins
Bittencourt, Leonardo Oliveira
Aragão, Walessa Alana Bragança
Souza, Michel Platini Caldas de
Silva, Marcia Cristina Freitas
Dionizio, Aline
Buzalaf, Marília Afonso Rabelo
Crespo-López, Maria Elena
Lima, Rafael Rodrigues
author_role author
author2 Ferreira, Maria Karolina Martins
Bittencourt, Leonardo Oliveira
Aragão, Walessa Alana Bragança
Souza, Michel Platini Caldas de
Silva, Marcia Cristina Freitas
Dionizio, Aline
Buzalaf, Marília Afonso Rabelo
Crespo-López, Maria Elena
Lima, Rafael Rodrigues
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Eiró, Luciana Guimarães
Ferreira, Maria Karolina Martins
Bittencourt, Leonardo Oliveira
Aragão, Walessa Alana Bragança
Souza, Michel Platini Caldas de
Silva, Marcia Cristina Freitas
Dionizio, Aline
Buzalaf, Marília Afonso Rabelo
Crespo-López, Maria Elena
Lima, Rafael Rodrigues
dc.subject.decsPrimary.pt_BR.fl_str_mv Sistema Nervoso Central
Intoxicação do Sistema Nervoso por Mercúrio
Mercúrio / toxicidade
Medula Espinal
Estresse Oxidativo
Proteômica
topic Sistema Nervoso Central
Intoxicação do Sistema Nervoso por Mercúrio
Mercúrio / toxicidade
Medula Espinal
Estresse Oxidativo
Proteômica
description Methylmercury (MeHg) is considered by the World Health Organization (WHO) as one of the chemicals of greatest public health concern. Although central nervous system (CNS) is the main target organ, the effects over the spinal cord are not well understood, especially in chronic exposure at similar doses to those faced by humans. This study aimed to investigate possible changes on global proteomic profile and oxidative biochemistry status of rats spinal cord, related to the maintenance and balance of the organism functioning, mimicking a human daily exposure by diet (chronic and with relatively low levels). For this, 28 adults male Wistar rats were divided into two groups: MeHg group, which was intoxicated by intragastric gavage with MeHg at a dose of 0.04 mg/kg/day for 60 days, and control group, that received only vehicle. After the exposure period, the spinal cords were collected for evaluation of total mercury levels, proteomic profile, with further bioinformatic overrepresentation analysis (ORA), and oxidative biochemistry, by analyzing the antioxidant capacity against peroxyl radicals (ACAP), lipid peroxidation (LPO), nitrite levels, measurement of Trolox Equivalent Antioxidant Capacity (TEAC) and Reduced Glutathione (GSH). The MeHg exposure increased total mercury levels in spinal cord parenchyma, which increased lipid peroxidation and nitrite levels, and reduced antioxidant status. The proteomic analysis showed several proteins related to biological processes, cellular components and molecular functions. Moreover, according to the ORA analysis, the proteins are involved in processes such as mitochondrial activity, stress response, cytoskeleton and apoptosis. Therefore, we concluded that exposure to low doses of MeHg can activate the oxidative stress pathway and thus, modulate the status of regulation of several important proteins.
publishDate 2020
dc.date.accessioned.fl_str_mv 2020-10-19T14:02:00Z
dc.date.available.fl_str_mv 2020-10-19T14:02:00Z
dc.date.issued.fl_str_mv 2020
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.citation.fl_str_mv EIRÓ, Luciana Guimarães et al. Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress. Food and Chemical Toxicology, v. 146, n. 111772, Dec. 2020.
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/4186
dc.identifier.issn.-.fl_str_mv 0278-6915
dc.identifier.doi.-.fl_str_mv 10.1016/j.fct.2020.111772
identifier_str_mv EIRÓ, Luciana Guimarães et al. Chronic methylmercury exposure causes spinal cord impairment: proteomic modulation and oxidative stress. Food and Chemical Toxicology, v. 146, n. 111772, Dec. 2020.
0278-6915
10.1016/j.fct.2020.111772
url https://patua.iec.gov.br/handle/iec/4186
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