ROLE OF THE ABCG2 TRANSPORTER AND ITS POLYMORPHISMS IN THE EXCRETION OF ANTIPARASITIC AGENTS AND PESTICIDES IN RUMINANT MILK (Q3170055): Difference between revisions
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ROLE OF THE ABCG2 TRANSPORTER AND ITS POLYMORPHISMS IN THE EXCRETION OF ANTIPARASITIC AGENTS AND PESTICIDES IN RUMINANT MILK | |||
Revision as of 03:32, 9 October 2021
Project Q3170055 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | ROLE OF THE ABCG2 TRANSPORTER AND ITS POLYMORPHISMS IN THE EXCRETION OF ANTIPARASITIC AGENTS AND PESTICIDES IN RUMINANT MILK |
Project Q3170055 in Spain |
Statements
66,550.0 Euro
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133,100.0 Euro
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50.0 percent
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1 January 2019
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31 December 2021
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UNIVERSIDAD DE LEON
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24089
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DE ENTRE LOS RETOS PROPUESTOS EN EL PROGRAMA HORIZONTE 2020 Y EN EL PLAN ESTATAL DE INVESTIGACION CIENTIFICA Y TECNICA DE INNOVACION 2017-2020, LA SEGURIDAD Y CALIDAD ALIMENTARIA CONSTITUYEN UNA PRIORIDAD. EN ESTE PROYECTO, PRETENDEMOS ESTUDIAR EL PAPEL DEL TRANSPORTADOR DE MEMBRANA ABCG2 DE RUMIANTES EN LA CONTAMINACION DE LA LECHE CON XENOBIOTICOS COMO ANTIPARASITARIOS Y PESTICIDAS, CON EL FIN DE MINIMIZAR LA PRESENCIA DE RESIDUOS DE FARMACOS. ESTA PROTEINA PARTICIPA EN LA SECRECION A LECHE DE DIVERSOS FARMACOS, TOXINAS Y NUTRIENTES Y SU ACTIVIDAD PUEDE PUEDE VERSE MODIFICADA DEBIDO AL GENOTIPO DEL ANIMAL O A LA CO-ADMINISTRACION DE COMPONENTES DE LA DIETA O FARMACOS QUE ACTUEN COMO INHIBIDORES. DESDE UN PUNTO DE VISTA VETERINARIO, EL POLIMORFISMO Y581S DEL ABCG2 BOVINO ES DE GRAN INTERES YA QUE EN LOS ANIMALES PORTADORES PRODUCE UNA MAYOR SECRECION DE FARMACOS, INCLUYENDO ANTIBIOTICOS Y ANTIINFLAMATORIOS. POR TANTO, EL PROPOSITO DE ESTE PROYECTO SERA EL ESTUDIO DE LA INTERACCION DE ABCG2 DE RUMIANTES CON FARMACOS AMPLIAMENTE UTILIZADOS EN TERAPEUTICA VETERINARIA COMO SON LOS ANTIPARASITARIOS, TALES COMO ANTIHELMINTICOS DE DIFERENTES GRUPOS QUIMICOS, Y CON PESTICIDAS ORGANICOS UTILIZADOS COMO INSECTICIDAS TALES COMO LOS PIRETROIDES. PRIMERO, SE UTILIZARAN CULTIVOS CELULARES QUE SOBREEXPRESAN LA VARIANTE OVINA Y LAS DOS VARIANTES BOVINAS DEL TRANSPORTADOR, PREVIAMENTE GENERADOS EN NUESTRO LABORATORIO. SE REALIZARAN EXPERIMENTOS DE TRANSPORTE TRANSEPITELIAL Y DE ACUMULACION DE MITOXANTRONA. SE ESTUDIARA EN CADA CASO LA POSIBLE INHIBICION E INTERACCIONES FARMACOLOGICAS MEDIADAS POR EL TRANSPORTADOR. DADO QUE LA ACTIVIDAD DEL TRANSPORTADOR REGULA LA TRANSFERENCIA DE COMPUESTOS A LA LECHE Y AFECTA A LA CALIDAD Y SEGURIDAD DE LA LECHE DE RUMIANTES, SE COMPROBARA EL EFECTO IN VIVO DE LOS COMPUESTOS IDENTIFICADOS IN VITRO, UTILIZANDO EL MODELO KNOCKOUT EN EL TRANSPORTADOR. POR ULTIMO, SE ANALIZARA POR PRIMERA VEZ LA CORRELACION LECHE/PLASMA DE LOS ANTIPARASITARIOS Y LOS PESTICIDAS EN VACAS PORTADORAS Y NO PORTADORAS DE LA VARIANTE Y581S, PARA EVALUAR LA POSIBLE SECRECION DIFERENCIAL A LA LECHE EN FUNCION DEL GENOTIPO DEL ANIMAL. CON LOS INHIBIDORES DEL TRANSPORTADOR QUE SE IDENTIFIQUEN, SE INCLUIRAN ENSAYOS DE INHIBICION DE LA SECRECION A LECHE EN OVEJAS Y EN GANADO VACUNO CON EL FIN DE CONTROLAR LOS RESIDUOS DE ANTIPARASITARIOS Y DE PESTICIDAS EN LECHE DE OVEJA Y DE VACA. ESTOS ESTUDIOS ESTABLECEN UN VINCULO ENTRE LA MEJORA DE LA PRODUCCION GANADERA Y LOS RETOS DE LA SOCIEDAD, CON LOS CORRESPONDIENTES BENEFICIOS PARA LA INDUSTRIA LACTEA, LOS AGRICULTORES Y TODA LA SOCIEDAD. (Spanish)
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PART OF THE CHALLENGES PROPOSED BY HORIZON 2020 PROGRAM AND PLAN ESTATAL DE INVESTIGACION CIENTIFICA Y TECNICA DE INNOVACION 2017-2020 INCLUDE FOOD SAFETY AND QUALITY AS PRIORITIES. IN THIS PROJECT, WE AIM TO STUDY THE ROLE OF THE MEMBRANE TRANSPORTER ABCG2 IN THE CONTAMINATION OF RUMINANT MILK WITH XENOBIOTICS SUCH AS ANTIPARASITIC DRUGS AND PESTICIDES IN ORDER TO MINIMIZE THE PRESENCE OF DRUG RESIDUES IN THIS FOOD. THIS PROTEIN PARTICIPATES IN THE MILK SECRETION OF SEVERAL DRUGS, TOXINS AND NUTRIENTS AND ITS ACTIVITY CAN BE CHANGED DUE TO THE ANIMAL GENOTYPE OR THE CONCOMITANT ADMINISTRATION OF DIETARY COMPONENTS OR DRUGS ACTING AS INHIBITORS. FROM THE VETERINARY POINT OF VIEW, THE PRESENCE OF THE Y581S POLYMORPHISM IN BOVINE ABCG2 IS OF GREAT INTEREST SINCE IT PRODUCES A HIGHER SECRETION OF DRUGS INCLUDING ANTIMICROBIAL AND ANTI-INFLAMMATORY AGENTS IN THE MILK OF CARRIER ANIMALS. THEREFORE, THE PURPOSE OF THIS PROJECT WILL BE TO STUDY THE IN VITRO AND IN VIVO INTERACTION OF RUMINANT ABCG2 WITH DRUGS WIDELY USED IN VETERINARY THERAPEUTICS NAMELY ANTIPARASITIC DRUGS, AS ANTHELMINTICS OF DIFFERENT CHEMICAL GROUPS, AND ORGANIC PESTICIDES USED AS INSECTICIDES SUCH AS PYRETHROIDS. FIRSTLY, STUDIES WILL BE PERFORMED IN VITRO USING CELL CULTURES, PREVIOUSLY GENERATED IN OTHER PROJECTS, WITH OVEREXPRESSION OF OVINE ABCG2 AND THE TWO BOVINE VARIANTS. TRANSEPITHELIAL TRANSPORT AND MITOXANTRONE ACCUMULATION ASSAYS WILL BE PERFORMED. THE POSSIBLE INHIBITION AND DRUG INTERACTIONS MEDIATED BY THE TRANSPORTER WILL BE STUDIED IN EACH CASE. THE ACTIVITY OF THE TRANSPORTER REGULATES THE TRANSFER OF COMPOUNDS INTO MILK THUS AFFECTING ITS QUALITY AND SAFETY. HENCE, THE COMPOUNDS IDENTIFIED IN VITRO WILL BE CHECKED IN VIVO USING THE KNOCKOUT MODEL OF THE TRANSPORTER. FINALLY, MILK/PLASMA CORRELATION WILL BE ANALYZED FOR ANTIPARASITIC DRUGS AND PESTICIDES IN Y581S CARRIER AND NON-CARRIER COWS FOR THE FIRST TIME, TO TEST A POTENTIAL DIFFERENTIAL SECRETION INTO MILK DEPENDING ON THE ANIMAL GENOTYPE. ASSAYS OF INHIBITION OF MILK SECRETION IN SHEEP AND CATTLE WILL BE INCLUDED, WHEN TRANSPORTER INHIBITORS ARE IDENTIFIED, WITH THE OBJECTIVE TO CONTROL MILK RESIDUES OF ANTIPARASITIC DRUGS AND PESTICIDES IN SHEEP AND CATTLE. THESE STUDIES LINK THE IMPROVEMENT OF LIVESTOCK PRODUCTION TO THE SOCIETY CHALLENGES WITH BENEFITS TO DAIRY INDUSTRY, FARMERS AND ALL THE SOCIETY. (English)
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León
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Identifiers
RTI2018-100903-B-I00
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