| spelling |
2023-11-16T21:26:36Z2023-11-16T21:26:36Z20221210https://doi.org/10.3390/metabo121009782218-1989http://hdl.handle.net/1843/61025https://orcid.org/0000-0001-9099-4843https://orcid.org/0000-0002-3090-7477https://orcid.org/0000-0001-6842-3016https://orcid.org/ 0000-0003-0840-0810Benzene is a human carcinogen whose exposure to concentrations below 1 ppm (3.19 mg·m−3) is associated with myelotoxic effects. The determination of biomarkers such as trans-trans muconic acid (AttM) and S-phenylmercapturic acid (SPMA) show exposure without reflecting the toxic effects of benzene. For this reason, in this study, the urinary metabolome of individuals exposed to low concentrations of benzene was investigated, with the aim of understanding the biological response to exposure to this xenobiotic and identifying metabolites correlated with the toxic effects induced by it. Ultra-efficient liquid chromatography coupled to a quadrupole-time-of-flight mass spectrometer (UHPLC-ESI-Q-ToF-MS) was used to identify metabolites in the urine of environmentally (n = 28) and occupationally exposed (n = 32) to benzene (mean of 22.1 μg·m−3 and 31.8 μg·m−3, respectively). Non-targeted metabolomics analysis by PLS-DA revealed nine urinary metabolites discriminating between groups and statistically correlated with oxidative damage (MDA, thiol) and genetic material (chromosomal aberrations) induced by the hydrocarbon. The analysis of metabolic pathways revealed important alterations in lipid metabolism. These results point to the involvement of alterations in lipid metabolism in the mechanisms of cytotoxic and genotoxic action of benzene. Furthermore, this study proves the potential of metabolomics to provide relevant information to understand the biological response to exposure to xenobiotics and identify early effect biomarkers.O benzeno é um carcinógeno humano cuja exposição a concentrações abaixo de 1 ppm (3,19 mg·m-3) está associada a efeitos mielotóxicos. A determinação de biomarcadores como ácido trans-trans mucônico (AttM) e ácido S-fenilmercaptúrico (SPMA) mostram exposição sem refletir os efeitos tóxicos do benzeno. Por esse motivo, neste estudo foi investigado o metaboloma urinário de indivíduos expostos a baixas concentrações de benzeno, com o objetivo de compreender a resposta biológica à exposição a esse xenobiótico e identificar metabólitos correlacionados com os efeitos tóxicos por ele induzidos. Cromatografia líquida ultraeficiente acoplada a um espectrômetro de massa quadrupolo de tempo de voo (UHPLC-ESI-Q-ToF-MS) foi usada para identificar metabólitos na urina de expostos ambientalmente (n = 28) e ocupacionalmente (n = 32 ) ao benzeno (média de 22,1 μg·m−3 e 31,8 μg·m−3, respectivamente). A análise metabolômica não direcionada por PLS-DA revelou nove metabólitos urinários discriminando entre grupos e correlacionados estatisticamente com dano oxidativo (MDA, tiol) e material genético (aberrações cromossômicas) induzidos pelo hidrocarboneto. A análise das vias metabólicas revelou alterações importantes no metabolismo lipídico. Estes resultados apontam para o envolvimento de alterações no metabolismo lipídico nos mecanismos de ação citotóxica e genotóxica do benzeno. Além disso, este estudo comprova o potencial da metabolômica em fornecer informações relevantes para compreender a resposta biológica à exposição a xenobióticos e identificar biomarcadores de efeito precoce.engUniversidade Federal de Minas GeraisUFMGBrasilFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASMetabolitesBenzenoMetabolômicaEcotoxicologiaToxicologiaCategorias de trabalhadoresBenzeneMetabolomic untargetedUHPLC-ESI-Q-TOF-MSEnvironmental toxicologyOccupational toxicologyMetabolomic study of urine from workers exposed to low concentrations of benzene by UHPLC-ESI-QToF-MS reveals potential biomarkers associated with Oxidative stress and genotoxicityMetabolomic study of urine from workers exposed to low concentrations of benzene by UHPLC-ESI-QToF-MS reveals potential biomarkers associated with Oxidative stress and genotoxicityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.mdpi.com/2218-1989/12/10/978Michele P. R. MendesMaria José N. PaivaIsabele C. Costa-AmaralLeandro V. B. CarvalhoVictor O. FigueiredoEline S. GonçalvesAriane L. LarentisLeiliane Coelho Andréapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/61025/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALMetabolomic study of urine from workers exposed to low concentrations of benzene by UHPLC-ESI-QToF-MS reveals potential biomarkers associated with Oxidative stress and genotoxicity.pdfMetabolomic study of urine from workers exposed to low concentrations of benzene by UHPLC-ESI-QToF-MS reveals potential biomarkers associated with Oxidative stress and genotoxicity.pdfapplication/pdf4965005https://repositorio.ufmg.br/bitstream/1843/61025/2/Metabolomic%20study%20of%20urine%20from%20workers%20exposed%20to%20low%20concentrations%20of%20benzene%20by%20UHPLC-ESI-QToF-MS%20reveals%20potential%20biomarkers%20associated%20with%20Oxidative%20stress%20and%20genotoxicity.pdf9ece4bb77e712b8ae52d2ab8607bd30eMD521843/610252023-11-16 18:26:36.518oai:repositorio.ufmg.br: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Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-11-16T21:26:36Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
|