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A importância do uso de métodos complementares para a avaliação da toxicidade de hidrocarbonetos aromáticos policíclicos
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Advisor(s)
Abstract(s)
Hidrocarbonetos Aromáticos Policíclicos (HAPs) e seus derivados Halogenados
(HHAPs) são conhecidos como um conjunto de contaminantes
ambientais, classificados como potencialmente tóxicos, mutagénicos e
carcinogénicos, sendo um assunto de extrema importância e preocupação
para a saúde pública. Diversos estudos têm reportado o potencial
efeito tóxico destes compostos após longos períodos de exposição, pelo
uso de métodos colorimétricos como o ensaio de brometo de 3-[4,5-
dimetil-tiazol-2-il]-2,5-difeniltetrazólio (MTT) e vermelho neutro. Contudo,
apesar de estes métodos clássicos de avaliação da citotoxicidade
in vitro permitirem, de forma rápida, identificar as propriedades nocivas
dos compostos, não permitem compreender os mecanismos moleculares
subjacentes responsáveis pela sua toxicidade. Deste modo, no presente
estudo, para avaliar os efeitos à exposição aos compostos Pireno
(Pir) e seu derivado resultante da desinfeção de águas por bromação,
1-BromoPireno (1-BrPir), foram utilizados outros métodos complementares
como avaliação do stress oxidativo e vários fenómenos associados
à morte celular programada. Os resultados obtidos comprovam não
só a existência de efeitos citotóxicos dos poluentes quando acumulados,
como também possíveis efeitos genotóxicos. Assim, pelos métodos
complementares, foi possível a identificação de alvos moleculares passiveis
de ação farmacológica, o que pode constituir o primeiro passo para
o desenho de estratégias terapêuticas que visem prevenir ou tratar os
danos provocados por estes poluentes no Homem.
Polycyclic Aromatic Hydrocarbons (PAHs) and their halogenated derivatives (HPAHs) are known as a set of environmental contaminants classified as potentially toxic, mutagenic and carcinogenic, being a matter of utmost importance and concern to public health. Several studies have reported the potential toxic effects of these compounds after long periods of exposure by the use of colorimetric methods such as 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red. Nonetheless, despite these classic in vitro cytotoxicity assays allow, in a faster way, the identification of the harmful properties of the compounds, they fail in elucidating the underlying molecular mechanisms responsible for their toxicity. Taking into account these mentioned aspects, in the present work, other complementary methods were used in order to evaluate the effects of the exposure to Pyrene (Pyr) and to a brominated-pyrene derivative (resulted from water disinfection), 1-BromoPyrene (1-BrPyr). Effectively, by the evaluation of the oxidative stress and programmed cell death induced by PAHs it was not only possible to verify the cytotoxic effects of PAHs when accumulated but also their potential genotoxic effects. In conclusion, through the use of other tests than the classic cytotoxicity assays, it was possible to identify potential druggable molecular targets which can be the first step towards the development of new therapeutic strategies either to prevent or treat the damage caused by these compounds in Humans.
Polycyclic Aromatic Hydrocarbons (PAHs) and their halogenated derivatives (HPAHs) are known as a set of environmental contaminants classified as potentially toxic, mutagenic and carcinogenic, being a matter of utmost importance and concern to public health. Several studies have reported the potential toxic effects of these compounds after long periods of exposure by the use of colorimetric methods such as 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red. Nonetheless, despite these classic in vitro cytotoxicity assays allow, in a faster way, the identification of the harmful properties of the compounds, they fail in elucidating the underlying molecular mechanisms responsible for their toxicity. Taking into account these mentioned aspects, in the present work, other complementary methods were used in order to evaluate the effects of the exposure to Pyrene (Pyr) and to a brominated-pyrene derivative (resulted from water disinfection), 1-BromoPyrene (1-BrPyr). Effectively, by the evaluation of the oxidative stress and programmed cell death induced by PAHs it was not only possible to verify the cytotoxic effects of PAHs when accumulated but also their potential genotoxic effects. In conclusion, through the use of other tests than the classic cytotoxicity assays, it was possible to identify potential druggable molecular targets which can be the first step towards the development of new therapeutic strategies either to prevent or treat the damage caused by these compounds in Humans.
Description
Keywords
Hidrocarbonetos Aromáticos Policíclicos HAPs Contaminantes Ambientais Contaminação de Águas Avaliação do Risco Toxicologia Água e Solo Saúde Ambiental Saúde Pública Polycyclic Aromatic Hydrocarbons PAHs Toxicity
Pedagogical Context
Citation
Boletim Epidemiológico Observações. 2016 maio-agosto;5(16):38-43
Publisher
Instituto Nacional de Saúde Doutor Ricardo Jorge, IP