Evaluación del riesgo ecotoxicológico de cinco parabenos mediante batería de bioensayos

[ES] Actualmente, una parte importante de la población mundial tiene problemas para acceder a un recurso tan esencial como es el agua. Y esto no ocurre por su escasez, sino por su calidad, la cual decae cada vez más por culpa de la contaminación. Ya sea desde efluentes industriales, agrícolas o urbanos, algunos compuestos contaminantes logran llegar a las aguas naturales de ríos o mares procedentes de las estaciones depuradoras de aguas residuales (EDARs), donde no se han podido eliminar. Entre estos compuestos destacan los microcontaminantes o contaminantes emergentes que, debido a las bajas concentraciones en las que se encuentran, pueden pasar inadvertidos en los controles de calidad del agua. Pese a sus bajas concentraciones, los efectos nocivos sobre la calidad del agua y la fauna que habita en ella son sustanciales. Dentro de los considerados microcontaminantes se encuentran los parabenos, muy empleados en la fabricación de productos cosméticos. Estos compuestos químicos suponen un riesgo importante para los ecosistemas acuáticos debido a su actividad estrogénica, actuando como disruptores endocrinos. En relación con las técnicas analíticas, se han conseguido importantes avances en la detección ambiental de los contaminantes emergentes y en el desarrollo de métodos más efectivos para su eliminación. En cuanto a las tecnologías desarrolladas, los Procesos de Oxidación Avanzada (POAs) se han consolidado como una eficiente alternativa para el tratamiento de aguas residuales, pues son muy efectivos en la eliminación de compuestos tóxicos de diversa naturaleza. Existen diferentes tipos de POAs, todos basados en la generación de radicales hidroxilo, y han supuesto una notable mejora en el ámbito de la depuración de aguas de las EDARs. Cuando se realizan tratamientos de aguas contaminadas mediante estas tecnologías es necesario analizar la eficacia de los mismos, determinando la toxicidad de las aguas tratadas y evaluando el riesgo ambiental que supondría su vertido, debido a la falta de información de la toxicidad de muchos metabolitos procedentes del tratamiento que escapan a las técnicas analíticas. Con este propósito, se llevan a cabo multitud de bioensayos con organismos procedentes de diversos niveles tróficos en la escala biológica que permiten evaluar la eficacia de los tratamientos mediante POAs y el impacto ecotoxicológico que podrían tener las aguas tratadas sobre un ecosistema natural. En este proyecto de investigación se realiza una evaluación ecotoxicológica de cinco parabenos (butilparabeno, etilparabeno, isobutilparabeno, metilparabeno y propilparabeno) a partir de los datos obtenidos en un estudio de toxicidad realizado para el proyecto Tecnologías avanzadas e híbridas para eliminación de contaminantes, microcontaminantes, reuso y revalorización en diferentes aguas residuales, incluyendo enfoques tecno-económicos (RTI2018-097997-B-C31-AR) . Estos datos han sido cedidos para la realización de este trabajo de investigación. El estudio de la toxicidad de los cinco parabenos realizado para el proyecto RTI2018-097997-B-C31-AR se ha basado en los protocolos UNE-EN ISO 11348-3:2009 (determinación de la inhibición de la bioluminiscencia de la bacteria marina Aliivibrio fischeri), UNE-EN ISO 8692:2004 (determinación de la inhibición del desarrollo del alga unicelular de agua dulce Pseudokirchneriella subcapitata), UNE-EN ISO 6341 (determinación de la inhibición de la movilidad del microcrustáceo Daphnia magna) y UNE-EN ISO 10993-5:2009 (ensayos de citoxicidad in vitro). Los datos cedidos, procedentes del estudio de toxicidad, se van a analizar estadísticamente, con el fin de calcular diferentes parámetros de toxicidad que se utilizarán en la evaluación del riesgo ecotoxicológico. En dicha evaluación se va a tomar como referencia el Real Decreto 817/2015, las Directivas 2018/840/UE,2000/60/EC y 2008/105/EC, la directriz DOCE NºL 161/9 (1994), los Índices de Ri[EN] Nowadays, a significant part of the world's population has problems accessing an essential resource such as water. This is not because of its scarcity, but because of its quality, which is increasingly declining due to pollution. Whether from industrial, agricultural or urban effluents, some polluting compounds manage to reach the natural waters of rivers or seas from wastewater treatment plants (WWTPs), where they have not been able to be eliminated. Among these compounds, micro-pollutants or emerging contaminants stand out, which, due to the low concentrations in which they are found, can go unnoticed in water quality controls. Despite their low concentrations, the harmful effects on water quality and the fauna that inhabits it are substantial. Parabens, which are widely used in the manufacture of cosmetic products, are considered to be micro-pollutants. These chemical compounds pose a significant risk to aquatic ecosystems due to their estrogenic activity, acting as endocrine disruptors. In relation to analytical techniques, important advances have been made in the environmental detection of emerging contaminants and in the development of more effective methods for their removal. Regarding the technologies developed, Advanced Oxidation Processes (POAs) have been consolidated as an efficient alternative for the treatment of wastewater, as they are very effective in eliminating toxic compounds of various kinds. There are different types of POAs, all based on the generation of hydroxyl radicals, and they have meant a notable improvement in the field of water treatment in WWTPs. When treating polluted water using these technologies, it is necessary to analyse their effectiveness, determining the toxicity of the treated water and evaluating the environmental risk that its discharge would imply, due to the lack of information on the toxicity of many metabolites from the treatment that escape the analytical techniques. For this purpose, a multitude of bioassays are carried out with organisms from different trophic levels on the biological scale that allow the effectiveness of the treatments by means of POAs and the ecotoxicological impact that the treated water could have on a natural ecosystem to be evaluated. In this research project, an ecotoxicological evaluation of five parabens (butylparaben, ethylparaben, isobutylparaben, methylparaben and propyl paraben) is performed based on the data obtained in a toxicity study carried out for the project "Advanced and hybrid technologies for the elimination of pollutants, micro-pollutants, reuse and revaluation in different wastewater, including techno-economic approaches (RTI2018-097997-B-C31-AR)". These data have been provided for this research work. The toxicity study of the five parabens performed for the project RTI2018-097997-B-C31-AR has been based on the protocols UNE-EN ISO 11348-3:2009 (determination of the bioluminescence inhibition of marine bacteria Aliivibrio fischeri), UNE-EN ISO 8692: 2004 (determination of the development inhibition of unicellular freshwater algae Pseudokirchneriella subcapitata), UNE-EN ISO 6341 (determination of the mobility inhibition of microcrustacean Daphnia magna) and UNE-EN ISO 10993-5:2009 (in vitro cytoxicity tests). The data provided from the toxicity study will be statistically analysed in order to calculate different toxicity parameters to be used in the ecotoxicological risk assessment. In this evaluation, the Royal Decree 817/2015, the Directives 2018/840/EU, 2000/60/EC and 2008/105/EC, the DOCE guideline NºL 161/9 (1994), the Risk Indexes according to the Vighi and Calamari model (1996) and predictive computer models will be taken as references.Rius Salvador, M. (2020). Evaluación del riesgo ecotoxicológico de cinco parabenos mediante batería de bioensayos. http://hdl.handle.net/10251/149890TFG

Identification of small molecules capable of enhancing viral membrane fusion

Abstract Several approaches have been developed to analyze the entry of highly pathogenic viruses. In this study, we report the implementation of a Bimolecular Multicellular Complementation (BiMuC) assay to safely and efficiently monitor SARS-CoV-2 S-mediated membrane fusion without the need for microscopy-based equipment. Using BiMuC, we screened a library of approved drugs and identified compounds that enhance S protein-mediated cell-cell membrane fusion. Among them, ethynylestradiol promotes the growth of SARS-CoV-2 and Influenza A virus in vitro. Our findings demonstrate the potential of BiMuC for identifying small molecules that modulate the life cycle of enveloped viruses, including SARS-CoV-2

Cetylpyridinium chloride and chlorhexidine show antiviral activity against Influenza A virus and Respiratory Syncytial virus in vitro.

BackgroundThe oral cavity is the site of entry and replication for many respiratory viruses. Furthermore, it is the source of droplets and aerosols that facilitate viral transmission. It is thought that appropriate oral hygiene that alters viral infectivity might reduce the spread of respiratory viruses and contribute to infection control.Materials and methodsHere, we analyzed the antiviral activity of cetylpyridinium chloride (CPC), chlorhexidine (CHX), and three commercial CPC and CHX-containing mouthwash preparations against the Influenza A virus and the Respiratory syncytial virus. To do so the aforementioned compounds and preparations were incubated with the Influenza A virus or with the Respiratory syncytial virus. Next, we analyzed the viability of the treated viral particles.ResultsOur results indicate that CPC and CHX decrease the infectivity of both the Influenza A virus and the Respiratory Syncytial virus in vitro between 90 and 99.9% depending on the concentration. Likewise, CPC and CHX-containing mouthwash preparations were up to 99.99% effective in decreasing the viral viability of both the Influenza A virus and the Respiratory syncytial virus in vitro.ConclusionThe use of a mouthwash containing CPC or CHX alone or in combination might represent a cost-effective measure to limit infection and spread of enveloped respiratory viruses infecting the oral cavity, aiding in reducing viral transmission. Our findings may stimulate future clinical studies to evaluate the effects of CPC and CHX in reducing viral respiratory transmissions

Identification of small molecules capable of enhancing viral membrane fusion

12 Pág.Several approaches have been developed to analyze the entry of highly pathogenic viruses. In this study, we report the implementation of a Bimolecular Multicellular Complementation (BiMuC) assay to safely and efficiently monitor SARS-CoV-2 S-mediated membrane fusion without the need for microscopy-based equipment. Using BiMuC, we screened a library of approved drugs and identified compounds that enhance S protein-mediated cell-cell membrane fusion. Among them, ethynylestradiol promotes the growth of SARS-CoV-2 and Influenza A virus in vitro. Our findings demonstrate the potential of BiMuC for identifying small molecules that modulate the life cycle of enveloped viruses, including SARS-CoV-2.This work was supported by the Generalitat Valenciana (PROMETEO/2019/065) and grant PID2020-119111GB-I00 by MCIN/AEI/10.13039/501100011033. O.Z. is funded by grant PID2020-114546RB by MCIN/AEI/10.13039/501100011033. L.G. is the recipient of a predoctoral contract (CIACIF/2021/119) from the Generatitat Valenciana. M.R-S is the recipient of a predoctoral contract from the Spanish Ministry of Science and Innovation (PRE2021-101042 by MCIN/AEI/10.13039/501100011033). This publication was also supported by the European Virus Archive GLOBAL (EVA-GLOBAL) project which has received funding from the European Union?s Horizon 2020 research and innovation program under grant agreement 871029.Peer reviewe