Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide

Autores
Hazelhoff, Maria Herminia; Trebucobich, Mara S.; Stoyanoff, Tania Romina; Chevalier, Alberto A.; Torres, Adriana Monica
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Inorganic mercury is a major environmental contaminant. The primary site of mercuryinduced injury is the kidney due to the uptake of Hg(2+) -conjugated organic anions in the proximal tubule, primary across the organic anion transporter 1 (Oat1) at the basolateral membrane. At the luminal side, mercuric ions are eliminated by the multidrug resistanceassociated protein 2 (Mrp2). It was described that furosemide treatment induces up-regulation of Oat1 renal expression. As novel preventive and therapeutic strategies based in pharmacological manipulation of drug transporters are emerging, this study was designed to evaluate the impact of furosemide modulation of Oat1 on the nephrotoxicity induced by HgCl2. Wistar rats were treated with furosemide (6 mg/100 g/ day, s.c.) during 4 days or with HgCl2 (4 mg/kg, i.p.) 18 h before the experiments or with furosemide during 4 days before the HgCl2 injection. Furosemide treatment improved HgCl2-induced tubular injury as assessed by urinary alkaline phosphatase activity, urinary glucose, Oat5 urinary excretion and histopathological studies. Besides, administration of furosemide enhanced mercury urinary excretion, reduced mercury total renal accumulation and increased Mrp2 renal expression. In summary, furosemide improves HgCl2- induced proximal tubule injury up-regulating mercury transporters and thus, increasing renal elimination of the mercuric ions. Hence, pharmacological manipulation of mercury transporters with furosemide might be a preventive strategy to reduce mercury toxicity.
Fil: Hazelhoff, Maria Herminia. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trebucobich, Mara S.. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina
Fil: Stoyanoff, Tania Romina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chevalier, Alberto A.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. GIHON Laboratorios Químicos; Argentina
Fil: Torres, Adriana Monica. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
MERCURIC CHLORIDE
FUROSEMIDE
ACUTE KIDNEY INJURY
MRP2
OAT1
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/13593
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/13593
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemideHazelhoff, Maria HerminiaTrebucobich, Mara S.Stoyanoff, Tania RominaChevalier, Alberto A.Torres, Adriana MonicaMERCURIC CHLORIDEFUROSEMIDEACUTE KIDNEY INJURYMRP2OAT1https://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Inorganic mercury is a major environmental contaminant. The primary site of mercuryinduced injury is the kidney due to the uptake of Hg(2+) -conjugated organic anions in the proximal tubule, primary across the organic anion transporter 1 (Oat1) at the basolateral membrane. At the luminal side, mercuric ions are eliminated by the multidrug resistanceassociated protein 2 (Mrp2). It was described that furosemide treatment induces up-regulation of Oat1 renal expression. As novel preventive and therapeutic strategies based in pharmacological manipulation of drug transporters are emerging, this study was designed to evaluate the impact of furosemide modulation of Oat1 on the nephrotoxicity induced by HgCl2. Wistar rats were treated with furosemide (6 mg/100 g/ day, s.c.) during 4 days or with HgCl2 (4 mg/kg, i.p.) 18 h before the experiments or with furosemide during 4 days before the HgCl2 injection. Furosemide treatment improved HgCl2-induced tubular injury as assessed by urinary alkaline phosphatase activity, urinary glucose, Oat5 urinary excretion and histopathological studies. Besides, administration of furosemide enhanced mercury urinary excretion, reduced mercury total renal accumulation and increased Mrp2 renal expression. In summary, furosemide improves HgCl2- induced proximal tubule injury up-regulating mercury transporters and thus, increasing renal elimination of the mercuric ions. Hence, pharmacological manipulation of mercury transporters with furosemide might be a preventive strategy to reduce mercury toxicity.Fil: Hazelhoff, Maria Herminia. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Trebucobich, Mara S.. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; ArgentinaFil: Stoyanoff, Tania Romina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Chevalier, Alberto A.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. GIHON Laboratorios Químicos; ArgentinaFil: Torres, Adriana Monica. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaRoyal Society of Chemistry2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/13593Hazelhoff, Maria Herminia; Trebucobich, Mara S.; Stoyanoff, Tania Romina; Chevalier, Alberto A.; Torres, Adriana Monica; Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide; Royal Society of Chemistry; Toxicology Research; 4; -1-2015; 1324-13322045-4538enginfo:eu-repo/semantics/altIdentifier/doi/10.1039/C5TX00100Einfo:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2015/TX/C5TX00100E#!divAbstractinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:01:00Zoai:ri.conicet.gov.ar:11336/13593instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:01:00.458CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
title Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
spellingShingle Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
Hazelhoff, Maria Herminia
MERCURIC CHLORIDE
FUROSEMIDE
ACUTE KIDNEY INJURY
MRP2
OAT1
title_short Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
title_full Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
title_fullStr Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
title_full_unstemmed Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
title_sort Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide
dc.creator.none.fl_str_mv Hazelhoff, Maria Herminia
Trebucobich, Mara S.
Stoyanoff, Tania Romina
Chevalier, Alberto A.
Torres, Adriana Monica
author Hazelhoff, Maria Herminia
author_facet Hazelhoff, Maria Herminia
Trebucobich, Mara S.
Stoyanoff, Tania Romina
Chevalier, Alberto A.
Torres, Adriana Monica
author_role author
author2 Trebucobich, Mara S.
Stoyanoff, Tania Romina
Chevalier, Alberto A.
Torres, Adriana Monica
author2_role author
author
author
author
dc.subject.none.fl_str_mv MERCURIC CHLORIDE
FUROSEMIDE
ACUTE KIDNEY INJURY
MRP2
OAT1
topic MERCURIC CHLORIDE
FUROSEMIDE
ACUTE KIDNEY INJURY
MRP2
OAT1
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Inorganic mercury is a major environmental contaminant. The primary site of mercuryinduced injury is the kidney due to the uptake of Hg(2+) -conjugated organic anions in the proximal tubule, primary across the organic anion transporter 1 (Oat1) at the basolateral membrane. At the luminal side, mercuric ions are eliminated by the multidrug resistanceassociated protein 2 (Mrp2). It was described that furosemide treatment induces up-regulation of Oat1 renal expression. As novel preventive and therapeutic strategies based in pharmacological manipulation of drug transporters are emerging, this study was designed to evaluate the impact of furosemide modulation of Oat1 on the nephrotoxicity induced by HgCl2. Wistar rats were treated with furosemide (6 mg/100 g/ day, s.c.) during 4 days or with HgCl2 (4 mg/kg, i.p.) 18 h before the experiments or with furosemide during 4 days before the HgCl2 injection. Furosemide treatment improved HgCl2-induced tubular injury as assessed by urinary alkaline phosphatase activity, urinary glucose, Oat5 urinary excretion and histopathological studies. Besides, administration of furosemide enhanced mercury urinary excretion, reduced mercury total renal accumulation and increased Mrp2 renal expression. In summary, furosemide improves HgCl2- induced proximal tubule injury up-regulating mercury transporters and thus, increasing renal elimination of the mercuric ions. Hence, pharmacological manipulation of mercury transporters with furosemide might be a preventive strategy to reduce mercury toxicity.
Fil: Hazelhoff, Maria Herminia. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Trebucobich, Mara S.. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina
Fil: Stoyanoff, Tania Romina. Universidad Nacional del Nordeste. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Chevalier, Alberto A.. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. GIHON Laboratorios Químicos; Argentina
Fil: Torres, Adriana Monica. Universidad Nacional de Rosario. Facultad de Cs.bioquimicas y Farmaceuticas. Departamento de Cs.fisiologicas. Area Farmacologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Inorganic mercury is a major environmental contaminant. The primary site of mercuryinduced injury is the kidney due to the uptake of Hg(2+) -conjugated organic anions in the proximal tubule, primary across the organic anion transporter 1 (Oat1) at the basolateral membrane. At the luminal side, mercuric ions are eliminated by the multidrug resistanceassociated protein 2 (Mrp2). It was described that furosemide treatment induces up-regulation of Oat1 renal expression. As novel preventive and therapeutic strategies based in pharmacological manipulation of drug transporters are emerging, this study was designed to evaluate the impact of furosemide modulation of Oat1 on the nephrotoxicity induced by HgCl2. Wistar rats were treated with furosemide (6 mg/100 g/ day, s.c.) during 4 days or with HgCl2 (4 mg/kg, i.p.) 18 h before the experiments or with furosemide during 4 days before the HgCl2 injection. Furosemide treatment improved HgCl2-induced tubular injury as assessed by urinary alkaline phosphatase activity, urinary glucose, Oat5 urinary excretion and histopathological studies. Besides, administration of furosemide enhanced mercury urinary excretion, reduced mercury total renal accumulation and increased Mrp2 renal expression. In summary, furosemide improves HgCl2- induced proximal tubule injury up-regulating mercury transporters and thus, increasing renal elimination of the mercuric ions. Hence, pharmacological manipulation of mercury transporters with furosemide might be a preventive strategy to reduce mercury toxicity.
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/13593
Hazelhoff, Maria Herminia; Trebucobich, Mara S.; Stoyanoff, Tania Romina; Chevalier, Alberto A.; Torres, Adriana Monica; Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide; Royal Society of Chemistry; Toxicology Research; 4; -1-2015; 1324-1332
2045-4538
url http://hdl.handle.net/11336/13593
identifier_str_mv Hazelhoff, Maria Herminia; Trebucobich, Mara S.; Stoyanoff, Tania Romina; Chevalier, Alberto A.; Torres, Adriana Monica; Amelioration of mercury nephrotoxicity after pharmacological manipulation of organic anion transporter 1 (Oat1) and multidrug associated resistance protein 2 (Mrp2) with furosemide; Royal Society of Chemistry; Toxicology Research; 4; -1-2015; 1324-1332
2045-4538
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1039/C5TX00100E
info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2015/TX/C5TX00100E#!divAbstract
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.48226

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