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Cellular and molecular mechanisms of hepatotoxicity and embryotoxicity by emerging contaminants decametilcyclopentasiloxane and triclopyr

Abstract

The massive use of agricultural inputs, pharmaceuticals and industrial chemicals, among other chemical substances, causes environmental contamination with bioaccumulation and biomagnification of their residues, which may lead to inadequate exposures and increase the incidence of human diseases. On the other hand, experimental studies have the capacity to predict the toxicity of these emerging contaminants, being valuable aids for understanding the biological mechanisms potentially involved in the risk to human health. Currently, the use of so-called alternative methods for assessing the toxicity of chemicals is an international trend in response to the 3R (reduce, refine, replace) policy that restricts the use of animals in research. Among the new alternative methodologies applied to toxicology are: 1) three-dimensional (3D) cell cultures for cell-based screening, which more accurately reproduce the tissue environment in vivo, unlike cell cultures in monolayers, and 2) the use of Danio rerio (zebrafish) as a model organism for high-throughput screening. These methodologies may contribute to elucidate possible mechanisms of toxicity of emerging environmental contaminants. For example, the 3D cell culture system allows the assessment of the potential for induction of mitochondrial dysfunctions, autophagy / mitofagia, degeneration and cell death, whereas the embryotoxicity potential can be evaluated when zebrafish is used in its early stages of development. This project, which puts us in line with the worldwide trend of using alternative methods to assess the risk of chemical compounds, aims to evaluate the toxicities of two environmental contaminants, the herbicide triclopyr and the product for personal use in cosmetics, decamethylcyclopentasiloxane (D5). The indicated experimental systems - three-dimensional culture of liver cells and zebrafish embryos exposed to environmental contaminants - will be supplemented by immunohistochemical analyzes of functional cell markers and by evaluation of expression of genes of interest by RT-qPCR, validated by western blot. The information collected may provide scientific support for the implementation of coherent and effective strategies to control these environmental contaminants. (AU)

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