STRATEGIES TO MITIGATE TOXICITY ASSOCIATED WITH CHRONIC EXPOSURE TO ARSENIC OR MERCURY THROUGH DIET (Q3159039)
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Project Q3159039 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | STRATEGIES TO MITIGATE TOXICITY ASSOCIATED WITH CHRONIC EXPOSURE TO ARSENIC OR MERCURY THROUGH DIET |
Project Q3159039 in Spain |
Statements
133,100.0 Euro
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266,200.0 Euro
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50.0 percent
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1 January 2019
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31 December 2022
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AGENCIA CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
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46190
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LA PRESENCIA DE METALES/METALOIDES, ESPECIALMENTE AS Y HG, EN AGUAS Y ALIMENTOS AFECTA A LA SALUD DE MILLONES DE PERSONAS. REDUCIR LA EXPOSICION Y MITIGAR LOS EFECTOS ADVERSOS DE ESTOS ELEMENTOS CONSTITUYE UN RETO EN EL CONTEXTO DE LA SEGURIDAD ALIMENTARIA Y REQUIERE DE UNA ADECUADA CARACTERIZACION DE SUS MECANISMOS DE TOXICIDAD. PESE A QUE EN LA MAYORIA DE LOS CASOS LA EXPOSICION A AS Y HG SE REALIZA A TRAVES DE LA DIETA, SE CONOCE MUY POCO SOBRE SUS EFECTOS EN LA MUCOSA Y LA MICROBIOTA INTESTINAL, LA POSIBLE ASOCIACION DE ESTA TOXICIDAD INTESTINAL CON LOS EFECTOS OBSERVADOS A NIVEL SISTEMICO Y LOS CAMBIOS EN LAS POBLACIONES MICROBIANAS Y SUS REPERCUSIONES PARA EL HUESPED. ADEMAS, LA MAYORIA DE LOS ESTUDIOS AL RESPECTO HAN UTILIZADO EXPOSICIONES AGUDAS O SUBCRONICAS, QUE DIFIEREN DE LA SITUACION REAL DE LAS POBLACIONES AFECTADAS._x000D_ ESTE PROYECTO SE PROPONE CUBRIR ESTE HUECO EN EL CONOCIMIENTO SOBRE EL MODO DE ACCION DE AS Y HG A NIVEL INTESTINAL, Y UTILIZARLO COMO BASE PARA EL DISEÑO DE ESTRATEGIAS DIETETICAS MAS EFICACES PARA REDUCIR EL DAÑO ASOCIADO A LA INGESTA CRONICA DE AS O HG. CON ESTE FIN, SE LLEVARA A CABO UN ESTUDIO DE LOS EFECTOS TOXICOS DE AMBOS ELEMENTOS TRAZA EN ROEDORES SOMETIDOS A EXPOSICION CRONICA. LA TOXICIDAD SOBRE LA MUCOSA SE ESTIMARA MIDIENDO LA PERMEABILIDAD INTESTINAL, MARCADORES DE INFLAMACION Y ESTRES OXIDATIVO, ASI COMO MEDIANTE UN EXAMEN HISTOLOGICO DE LA MUCOSA. LA EVOLUCION DE LA MICROBIOTA INTESTINAL SE LLEVARA A CABO MEDIANTE SECUENCIACION MASIVA DE MUESTRAS FECALES OBTENIDAS A LO LARGO DEL ENSAYO. CON EL FIN DE TENER UNA VISION MAS COMPLETA DE LA TOXICIDAD ASOCIADA A LOS TRATAMIENTOS ENSAYADOS Y DETERMINAR SI EXISTE ALGUNA ASOCIACION ENTRE LOS EFECTOS INTESTINALES Y SISTEMICOS, SE ESTIMARA LA TOXICIDAD SISTEMICA MEDIANTE LA DETERMINACION DE MARCADORES RENALES, HEPATICOS, INMUNOLOGICOS Y LA EVALUACION HISTOLOGICA DE LOS ORGANOS DIANA. ADEMAS, CON EL FIN DE EVALUAR LOS EFECTOS DE LOS CAMBIOS DE LA MICROBIOTA INDUCIDOS POR LA EXPOSICION A AS O HG SOBRE LA FISIOLOGIA DEL HUESPED, SE PLANTEA LLEVAR A CABO ENSAYOS DE TRASPLANTE FECAL DE MICROBIOTA OBTENIDA DE ANIMALES DISBIOTICOS A RECEPTORES SANOS. LA PUESTA A PUNTO DE ESTAS METODOLOGIAS PROPORCIONARA AL GRUPO POTENTES HERRAMIENTAS PARA FUTUROS ESTUDIOS._x000D_ EL CONOCIMIENTO ADQUIRIDO, COMBINADO CON LOS RESULTADOS OBTENIDOS EN NUESTRO PROYECTO ANTERIOR, SERVIRA COMO BASE PARA EL ENSAYO DE ESTRATEGIAS ORIENTADAS A REDUCIR LA TOXICIDAD DE AS Y HG. ESTOS ENSAYOS SE REALIZARAN EN MODELOS ANIMALES SOMETIDOS A EXPOSICION CRONICA Y SUPLEMENTADOS CON LAS CEPAS DE BACTERIAS LACTICAS SELECCIONADAS, EN LOS QUE SE EVALUARAN LOS PARAMETROS DE TOXICIDAD INTESTINAL (INCLUIDA LA MICROBIOTA) Y SISTEMICA ANTERIORMENTE CITADOS._x000D_ LOS RESULTADOS OBTENIDOS PERMITIRAN OBTENER UN CONOCIMIENTO MAS COMPLETO DE LA TOXICIDAD ASOCIADA A LA EXPOSICION A AS O HG Y LA SELECCION DE ESTRATEGIAS DIETETICAS QUE PUEDEN SER IMPLEMENTADAS PARA SU FUTURA APLICACION EN POBLACIONES AFECTADAS PARA DISMINUIR EL RIESGO ASOCIADO A LA EXPOSICION A ESTOS ELEMENTOS, TAL Y COMO RECOMIENDAN ORGANISMOS OFICIALES COMO EFSA O JEFCA. (Spanish)
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PRESENCE OF METALS/METALLOIDS, ESPECIALLY AS AND HG, IN DRINKING WATER AND FOOD, COMPROMISES THE HEALTH STATUS OF MILLIONS OF PERSONS. DECREASING EXPOSURE AND MITIGATING THEIR TOXIC EFFECTS IS A CHALLENGE IN FOOD SAFETY THAT DEMANDS A THOROUGH CHARACTERIZATION OF THEIR MECHANISMS OF TOXICITY. HOWEVER, DESPITE EXPOSURE TO AS AND HG IS MAINLY ASSOCIATED TO THE CONSUMPTION OF CONTAMINATED WATER OR FOOD, LITTLE IS KNOWN ABOUT THEIR TOXIC EFFECTS ON THE INTESTINAL MUCOSA AND ITS ASSOCIATED MICROBIOTA, THE POSSIBLE LINK BETWEEN INTESTINAL TOXICITY AND SYSTEMIC EFFECTS, AND THE CHANGES IN THE GUT MICROBIAL AND THEIR CONSEQUENCES FOR THE HOST. FURTHERMORE, MOST STUDIES CARRIED OUT SO FAR HAVE STUDIED ACUTE OR SUBCHRONIC EXPOSURES, WHEREAS ACTUALLY, CHRONIC EXPOSURE IS PREVALENT IN MOST CASES._x000D_ THIS PROJECT AIMS TO FILL THIS KNOWLEDGE GAP CONCERNING THE MECHANISM OF TOXICITY OF AS AND HG AND TO USE THIS KNOWLEDGE TO DEVISE DIETARY STRATEGIES EFFECTIVE IN DIMINISHING THE DAMAGE ASSOCIATED TO CHRONIC INGESTION OF WATER OR FOOD CONTAINING AS OR HG. TO THIS END, TOXICITY OF AS OR HG WILL BE EVALUATED IN RODENTS SUBJECTED TO CHRONIC EXPOSURE. MUCOSAL TOXICITY WILL BE ESTIMATED BY MEASURING INTESTINAL PERMEABILITY, KNOWN MARKERS OF INFLAMMATION AND OXIDATIVE STRESS, AND HISTOLOGICAL EXAMINATION OF THE MUCOSA. EVOLUTION OF THE GUT MICROBIOTA WILL BE EVALUATED BY MASSIVE SEQUENCING OF FECAL SAMPLES COLLECTED DURING THE ASSAY. IN ORDER TO OBTAIN A COMPREHENSIVE VIEW OF THE TOXICITY ASSOCIATED TO THE ASSAYED TREATMENTS AND TO DETERMINE WHETHER A LINK EXISTS BETWEEN INTESTINAL DAMAGE AND SYSTEMIC EFFECTS, SYSTEMIC TOXICITY WILL ALSO BE ESTIMATED. CHARACTERIZED MARKERS WILL BE DETERMINED IN SERUM, LIVER AND KIDNEY SAMPLES AS WELL AS HISTOLOGICAL EXAMINATION OF THE TARGET ORGANS. FURTHERMORE, IN ORDER TO EVALUATE THE EFFECTS OF THE CHANGES INDUCED BY AS OR HG IN THE MICROBIOTA, AN APPROACH BASED ON FECAL TRANSPLANTS FROM DYSBIOTIC SUBJECTS TO HEALTHY RECEPTORS IS PROPOSED. AS INDICATED ABOVE, MUCOSAL AND SYSTEMIC TOXICITY MARKERS WILL BE MONITORED, AS WELL AS THE EVOLUTION OF THE TRANSPLANTED MICROBIOTA. THE ACQUISITION OF THESE TECHNIQUES WILL PROVIDE THE RESEARCH TEAM WITH POWERFUL TOOLS FOR FUTURE STUDIES._x000D_ KNOWLEDGE ACQUIRED IN THIS STUDY TOGETHER WITH THE RESULTS OBTAINED IN OUR PREVIOUS PROJECT WILL BE THE BASIS FOR THE ASSAY OF DIETARY STRATEGIES AIMED TO DECREASE THE TOXICITY OF AS AND HG. THESE ASSAYS WILL BE CARRIED OUT IN ANIMAL MODELS SUBJECTED TO CHRONIC EXPOSURE AND SUPPLEMENTED WITH SELECTED LACTIC ACID BACTERIA STRAINS. ITS EFFICACY WILL BE ESTIMATED BY DETERMINING INTESTINAL (INCLUDING MICROBIOTA) AND SYSTEMIC MARKERS OF TOXICITY._x000D_ THE RESULTS OBTAINED WILL PROVIDE A MORE COMPREHENSIVE KNOWLEDGE OF THE TOXICITY ASSOCIATED TO AS OR HG EXPOSURE AND THE SELECTION OF DIETARY STRATEGIES THAT CAN BE IMPLEMENTED FOR FUTURE APPLICATION IN EXPOSED POPULATIONS. THIS ACHIEVEMENT WILL PROVIDE A MEANS TO DECREASE THE RISK ASSOCIATED TO EXPOSURE TO AS OR HG, AS RECOMMENDED BY OFFICIAL AGENCIES SUCH AS EFSA OR JEFCA. (English)
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Paterna
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Identifiers
RTI2018-098071-B-I00
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