Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats

Autores
Severin, María Julia; Campagno, Romina Valeria; Brandoni, Anabel; Torres, Adriana Mónica
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Methotrexate (MTX) is commonly used in the treatment of malignant diseases and autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on the kidneys. Discovery of new biomarkers is required to improve the early detection of renal damage and optimize the effectiveness of treatments. The aim of this study was to evaluate the time course of MTX-induced nephrotoxicity and to compare the urinary excretion of the organic anion transporter 5 (uOat5) with alterations in other markers of renal function, and to elucidate the possible molecular mechanisms involved in uOat5. Animals were exposed to a unique dose of MTX (80 mg/kg body weight, intraperitoneal). Experiments were carried out at days 2, 4, 8 or 14 after MTX administration. Markers of renal damage, such as creatinine and urea plasma levels, urinary activity of alkaline phosphatase, microalbuminuria, urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) and histopathology, were evaluated. Renal organic anion transporter 5 (Oat5) expression and its presence in different urine fraction were assessed by western blotting. uOat5 was significantly increased 2 days after MTX treatment, before than any alteration in other parameters of kidney injury or renal morphology occurred. uNGAL showed an inverted pattern of urinary excretion compared to uOat5. Exosomal pathway is involved in the urinary excretion of Oat5 and depends on the degree of damage induced by MTX. These experimental data allow proposing uOat5 as a potential non-invasive biomarker for early detection of MTX-induced nephrotoxicity.
Fil: Severin, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Campagno, Romina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Brandoni, Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Torres, Adriana Mónica. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Materia
BIOMARKERS
KIDNEY INJURY
METHOTREXATE
ORGANIC ANION TRANSPORTER 5
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/114167
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in ratsSeverin, María JuliaCampagno, Romina ValeriaBrandoni, AnabelTorres, Adriana MónicaBIOMARKERSKIDNEY INJURYMETHOTREXATEORGANIC ANION TRANSPORTER 5https://purl.org/becyt/ford/3.5https://purl.org/becyt/ford/3Methotrexate (MTX) is commonly used in the treatment of malignant diseases and autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on the kidneys. Discovery of new biomarkers is required to improve the early detection of renal damage and optimize the effectiveness of treatments. The aim of this study was to evaluate the time course of MTX-induced nephrotoxicity and to compare the urinary excretion of the organic anion transporter 5 (uOat5) with alterations in other markers of renal function, and to elucidate the possible molecular mechanisms involved in uOat5. Animals were exposed to a unique dose of MTX (80 mg/kg body weight, intraperitoneal). Experiments were carried out at days 2, 4, 8 or 14 after MTX administration. Markers of renal damage, such as creatinine and urea plasma levels, urinary activity of alkaline phosphatase, microalbuminuria, urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) and histopathology, were evaluated. Renal organic anion transporter 5 (Oat5) expression and its presence in different urine fraction were assessed by western blotting. uOat5 was significantly increased 2 days after MTX treatment, before than any alteration in other parameters of kidney injury or renal morphology occurred. uNGAL showed an inverted pattern of urinary excretion compared to uOat5. Exosomal pathway is involved in the urinary excretion of Oat5 and depends on the degree of damage induced by MTX. These experimental data allow proposing uOat5 as a potential non-invasive biomarker for early detection of MTX-induced nephrotoxicity.Fil: Severin, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; ArgentinaFil: Campagno, Romina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; ArgentinaFil: Brandoni, Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; ArgentinaFil: Torres, Adriana Mónica. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; ArgentinaWiley Blackwell Publishing, Inc2019-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/114167Severin, María Julia; Campagno, Romina Valeria; Brandoni, Anabel; Torres, Adriana Mónica; Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats; Wiley Blackwell Publishing, Inc; Clinical and Experimental Pharmacology and Physiology; 46; 9; 6-2019; 828-8360305-1870CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/1440-1681.13122info:eu-repo/semantics/altIdentifier/doi/10.1111/1440-1681.13122info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:10:21Zoai:ri.conicet.gov.ar:11336/114167instacron: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 13:10:21.875CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
title Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
spellingShingle Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
Severin, María Julia
BIOMARKERS
KIDNEY INJURY
METHOTREXATE
ORGANIC ANION TRANSPORTER 5
title_short Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
title_full Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
title_fullStr Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
title_full_unstemmed Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
title_sort Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats
dc.creator.none.fl_str_mv Severin, María Julia
Campagno, Romina Valeria
Brandoni, Anabel
Torres, Adriana Mónica
author Severin, María Julia
author_facet Severin, María Julia
Campagno, Romina Valeria
Brandoni, Anabel
Torres, Adriana Mónica
author_role author
author2 Campagno, Romina Valeria
Brandoni, Anabel
Torres, Adriana Mónica
author2_role author
author
author
dc.subject.none.fl_str_mv BIOMARKERS
KIDNEY INJURY
METHOTREXATE
ORGANIC ANION TRANSPORTER 5
topic BIOMARKERS
KIDNEY INJURY
METHOTREXATE
ORGANIC ANION TRANSPORTER 5
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Methotrexate (MTX) is commonly used in the treatment of malignant diseases and autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on the kidneys. Discovery of new biomarkers is required to improve the early detection of renal damage and optimize the effectiveness of treatments. The aim of this study was to evaluate the time course of MTX-induced nephrotoxicity and to compare the urinary excretion of the organic anion transporter 5 (uOat5) with alterations in other markers of renal function, and to elucidate the possible molecular mechanisms involved in uOat5. Animals were exposed to a unique dose of MTX (80 mg/kg body weight, intraperitoneal). Experiments were carried out at days 2, 4, 8 or 14 after MTX administration. Markers of renal damage, such as creatinine and urea plasma levels, urinary activity of alkaline phosphatase, microalbuminuria, urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) and histopathology, were evaluated. Renal organic anion transporter 5 (Oat5) expression and its presence in different urine fraction were assessed by western blotting. uOat5 was significantly increased 2 days after MTX treatment, before than any alteration in other parameters of kidney injury or renal morphology occurred. uNGAL showed an inverted pattern of urinary excretion compared to uOat5. Exosomal pathway is involved in the urinary excretion of Oat5 and depends on the degree of damage induced by MTX. These experimental data allow proposing uOat5 as a potential non-invasive biomarker for early detection of MTX-induced nephrotoxicity.
Fil: Severin, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Campagno, Romina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Brandoni, Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
Fil: Torres, Adriana Mónica. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmaceuticas. Departamento de Ciencias Fisiológicas. Area Farmacología; Argentina
description Methotrexate (MTX) is commonly used in the treatment of malignant diseases and autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on the kidneys. Discovery of new biomarkers is required to improve the early detection of renal damage and optimize the effectiveness of treatments. The aim of this study was to evaluate the time course of MTX-induced nephrotoxicity and to compare the urinary excretion of the organic anion transporter 5 (uOat5) with alterations in other markers of renal function, and to elucidate the possible molecular mechanisms involved in uOat5. Animals were exposed to a unique dose of MTX (80 mg/kg body weight, intraperitoneal). Experiments were carried out at days 2, 4, 8 or 14 after MTX administration. Markers of renal damage, such as creatinine and urea plasma levels, urinary activity of alkaline phosphatase, microalbuminuria, urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) and histopathology, were evaluated. Renal organic anion transporter 5 (Oat5) expression and its presence in different urine fraction were assessed by western blotting. uOat5 was significantly increased 2 days after MTX treatment, before than any alteration in other parameters of kidney injury or renal morphology occurred. uNGAL showed an inverted pattern of urinary excretion compared to uOat5. Exosomal pathway is involved in the urinary excretion of Oat5 and depends on the degree of damage induced by MTX. These experimental data allow proposing uOat5 as a potential non-invasive biomarker for early detection of MTX-induced nephrotoxicity.
publishDate 2019
dc.date.none.fl_str_mv 2019-06
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/11336/114167
Severin, María Julia; Campagno, Romina Valeria; Brandoni, Anabel; Torres, Adriana Mónica; Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats; Wiley Blackwell Publishing, Inc; Clinical and Experimental Pharmacology and Physiology; 46; 9; 6-2019; 828-836
0305-1870
CONICET Digital
CONICET
url http://hdl.handle.net/11336/114167
identifier_str_mv Severin, María Julia; Campagno, Romina Valeria; Brandoni, Anabel; Torres, Adriana Mónica; Time evolution of methotrexate-induced kidney injury: A comparative study between different biomarkers of renal damage in rats; Wiley Blackwell Publishing, Inc; Clinical and Experimental Pharmacology and Physiology; 46; 9; 6-2019; 828-836
0305-1870
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/1440-1681.13122
info:eu-repo/semantics/altIdentifier/doi/10.1111/1440-1681.13122
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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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