The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury

Autores
Severin, María Julia; Trebucobich, Mara S.; Buszniez, Patricia Andrea; Brandoni, Anabel; Torres, Adriana Monica
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Methotrexate (MTX) belongs to a group of medicines known as antimetabolites. It is commonly used in the treatment of malignant diseases and is prescribed in autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on several organs, including the kidney. The organic anion transporter 5 (Oat5) is exclusively localized in the renal apical membrane. Oat5 urinary excretion was proposed as an early biomarker in ischemic and nephrotoxic-induced kidney injury and in renal damage due to vascular calcification in preclinical models. The aim of this study was to evaluate Oat5 renal expression and urinary excretion in rats 48 h after the exposure to different doses of MTX, in comparison with traditional markers of renal injury, such as creatinine and urea plasma levels, protein urinary levels, urinary alkaline phosphatase (AP) activity, fractional excretion of water (FEWater) and renal histology. Male Wistar rats were treated with a single intraperitoneal injection of MTX at different dosages: 40-80-120-180-360 mg per kg b.w. (M40, M80, M120, M180, M360, n = 4, respectively) and experiments were carried out 48 h after MTX administration. Oat5 renal expression was evaluated by western blotting and immunohistochemistry. Traditional parameters were only modified at the higher MTX dose (M360). Conversely, Oat5 urinary excretion was elevated at the middle dose of 80 mg per kg b.w. Oat5 renal expression was modified at the highest dose as well, both in homogenates and in apical membranes. These results suggest that Oat5 urinary excretion might serve as an early biomarker of MTX-induced kidney injury.
Fil: Severin, María Julia. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Trebucobich, Mara S.. Universidad Nacional de Rosario; Argentina
Fil: Buszniez, Patricia Andrea. Universidad Nacional de Rosario; Argentina
Fil: Brandoni, Anabel. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Torres, Adriana Monica. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Materia
METHOTREXATE
KIDNEY DAMAGE
BIOMARKERS
OAT5
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:11336/180036
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/180036
network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injurySeverin, María JuliaTrebucobich, Mara S.Buszniez, Patricia AndreaBrandoni, AnabelTorres, Adriana MonicaMETHOTREXATEKIDNEY DAMAGEBIOMARKERSOAT5https://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Methotrexate (MTX) belongs to a group of medicines known as antimetabolites. It is commonly used in the treatment of malignant diseases and is prescribed in autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on several organs, including the kidney. The organic anion transporter 5 (Oat5) is exclusively localized in the renal apical membrane. Oat5 urinary excretion was proposed as an early biomarker in ischemic and nephrotoxic-induced kidney injury and in renal damage due to vascular calcification in preclinical models. The aim of this study was to evaluate Oat5 renal expression and urinary excretion in rats 48 h after the exposure to different doses of MTX, in comparison with traditional markers of renal injury, such as creatinine and urea plasma levels, protein urinary levels, urinary alkaline phosphatase (AP) activity, fractional excretion of water (FEWater) and renal histology. Male Wistar rats were treated with a single intraperitoneal injection of MTX at different dosages: 40-80-120-180-360 mg per kg b.w. (M40, M80, M120, M180, M360, n = 4, respectively) and experiments were carried out 48 h after MTX administration. Oat5 renal expression was evaluated by western blotting and immunohistochemistry. Traditional parameters were only modified at the higher MTX dose (M360). Conversely, Oat5 urinary excretion was elevated at the middle dose of 80 mg per kg b.w. Oat5 renal expression was modified at the highest dose as well, both in homogenates and in apical membranes. These results suggest that Oat5 urinary excretion might serve as an early biomarker of MTX-induced kidney injury.Fil: Severin, María Julia. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Trebucobich, Mara S.. Universidad Nacional de Rosario; ArgentinaFil: Buszniez, Patricia Andrea. Universidad Nacional de Rosario; ArgentinaFil: Brandoni, Anabel. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Torres, Adriana Monica. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaRoyal Society of Chemistry2016-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/180036Severin, María Julia; Trebucobich, Mara S.; Buszniez, Patricia Andrea; Brandoni, Anabel; Torres, Adriana Monica; The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury; Royal Society of Chemistry; Toxicology Research; 5; 2; 1-2016; 530-5382045-452X2045-4538CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1039/C5TX00436Einfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:11:21Zoai:ri.conicet.gov.ar:11336/180036instacron: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:34982025-09-03 10:11:21.567CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
title The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
spellingShingle The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
Severin, María Julia
METHOTREXATE
KIDNEY DAMAGE
BIOMARKERS
OAT5
title_short The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
title_full The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
title_fullStr The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
title_full_unstemmed The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
title_sort The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury
dc.creator.none.fl_str_mv Severin, María Julia
Trebucobich, Mara S.
Buszniez, Patricia Andrea
Brandoni, Anabel
Torres, Adriana Monica
author Severin, María Julia
author_facet Severin, María Julia
Trebucobich, Mara S.
Buszniez, Patricia Andrea
Brandoni, Anabel
Torres, Adriana Monica
author_role author
author2 Trebucobich, Mara S.
Buszniez, Patricia Andrea
Brandoni, Anabel
Torres, Adriana Monica
author2_role author
author
author
author
dc.subject.none.fl_str_mv METHOTREXATE
KIDNEY DAMAGE
BIOMARKERS
OAT5
topic METHOTREXATE
KIDNEY DAMAGE
BIOMARKERS
OAT5
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Methotrexate (MTX) belongs to a group of medicines known as antimetabolites. It is commonly used in the treatment of malignant diseases and is prescribed in autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on several organs, including the kidney. The organic anion transporter 5 (Oat5) is exclusively localized in the renal apical membrane. Oat5 urinary excretion was proposed as an early biomarker in ischemic and nephrotoxic-induced kidney injury and in renal damage due to vascular calcification in preclinical models. The aim of this study was to evaluate Oat5 renal expression and urinary excretion in rats 48 h after the exposure to different doses of MTX, in comparison with traditional markers of renal injury, such as creatinine and urea plasma levels, protein urinary levels, urinary alkaline phosphatase (AP) activity, fractional excretion of water (FEWater) and renal histology. Male Wistar rats were treated with a single intraperitoneal injection of MTX at different dosages: 40-80-120-180-360 mg per kg b.w. (M40, M80, M120, M180, M360, n = 4, respectively) and experiments were carried out 48 h after MTX administration. Oat5 renal expression was evaluated by western blotting and immunohistochemistry. Traditional parameters were only modified at the higher MTX dose (M360). Conversely, Oat5 urinary excretion was elevated at the middle dose of 80 mg per kg b.w. Oat5 renal expression was modified at the highest dose as well, both in homogenates and in apical membranes. These results suggest that Oat5 urinary excretion might serve as an early biomarker of MTX-induced kidney injury.
Fil: Severin, María Julia. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Trebucobich, Mara S.. Universidad Nacional de Rosario; Argentina
Fil: Buszniez, Patricia Andrea. Universidad Nacional de Rosario; Argentina
Fil: Brandoni, Anabel. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Torres, Adriana Monica. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
description Methotrexate (MTX) belongs to a group of medicines known as antimetabolites. It is commonly used in the treatment of malignant diseases and is prescribed in autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on several organs, including the kidney. The organic anion transporter 5 (Oat5) is exclusively localized in the renal apical membrane. Oat5 urinary excretion was proposed as an early biomarker in ischemic and nephrotoxic-induced kidney injury and in renal damage due to vascular calcification in preclinical models. The aim of this study was to evaluate Oat5 renal expression and urinary excretion in rats 48 h after the exposure to different doses of MTX, in comparison with traditional markers of renal injury, such as creatinine and urea plasma levels, protein urinary levels, urinary alkaline phosphatase (AP) activity, fractional excretion of water (FEWater) and renal histology. Male Wistar rats were treated with a single intraperitoneal injection of MTX at different dosages: 40-80-120-180-360 mg per kg b.w. (M40, M80, M120, M180, M360, n = 4, respectively) and experiments were carried out 48 h after MTX administration. Oat5 renal expression was evaluated by western blotting and immunohistochemistry. Traditional parameters were only modified at the higher MTX dose (M360). Conversely, Oat5 urinary excretion was elevated at the middle dose of 80 mg per kg b.w. Oat5 renal expression was modified at the highest dose as well, both in homogenates and in apical membranes. These results suggest that Oat5 urinary excretion might serve as an early biomarker of MTX-induced kidney injury.
publishDate 2016
dc.date.none.fl_str_mv 2016-01
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/11336/180036
Severin, María Julia; Trebucobich, Mara S.; Buszniez, Patricia Andrea; Brandoni, Anabel; Torres, Adriana Monica; The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury; Royal Society of Chemistry; Toxicology Research; 5; 2; 1-2016; 530-538
2045-452X
2045-4538
CONICET Digital
CONICET
url http://hdl.handle.net/11336/180036
identifier_str_mv Severin, María Julia; Trebucobich, Mara S.; Buszniez, Patricia Andrea; Brandoni, Anabel; Torres, Adriana Monica; The urinary excretion of an organic anion transporter as an early biomarker of methotrexate-induced kidney injury; Royal Society of Chemistry; Toxicology Research; 5; 2; 1-2016; 530-538
2045-452X
2045-4538
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1039/C5TX00436E
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
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 13.13397

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