Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney

[EN] 1. We investigated the simultaneous effects of cyclosporine A (CsA) treatment in rats on glutathione metabolism, oxidative status and their interorgan relationship in the liver and kidney. 2. Reduced and oxidized glutathione (GSH and GSSG, respectively), lipid peroxidation and the activity of s...

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Autores: Jiménez Fernández, Rafael, Galán Hernández, Ana Isabel, González de Buitrago Arriero, José Manuel, Palomero Labajos, Jesús, Muñoz Bermejo, María Eugenia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2008
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/153875
Acceso en línea:http://hdl.handle.net/10366/153875
Access Level:acceso abierto
Palabra clave:Tratamiento
Metabolismo
Investigación clínica
Medicamentos
Lipid peroxidation
Oxidative stress
Cyclosporine A
Glutathione
Metabolism
Cyclosporine
3209 Farmacología
glutatión
ciclosporina
metabolismo
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oai_identifier_str oai:gredos.usal.es:10366/153875
network_acronym_str ES
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spelling Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And KidneyJiménez Fernández, RafaelGalán Hernández, Ana IsabelGonzález de Buitrago Arriero, José ManuelPalomero Labajos, JesúsMuñoz Bermejo, María EugeniaTratamientoMetabolismoInvestigación clínicaMedicamentosLipid peroxidationOxidative stressCyclosporine AGlutathioneMetabolismCyclosporineGlutathione3209 Farmacologíaglutatiónciclosporinametabolismo[EN] 1. We investigated the simultaneous effects of cyclosporine A (CsA) treatment in rats on glutathione metabolism, oxidative status and their interorgan relationship in the liver and kidney. 2. Reduced and oxidized glutathione (GSH and GSSG, respectively), lipid peroxidation and the activity of several enzymes of the glutathione cycle were evaluated in adult Wistar rats treated daily (i.p.) with saline, CsA vehicle (olive oil) or CsA (10 and 20 mg/kg per day) for either 1 or 4 weeks (short- and long-term treatments, respectively). 3. Cyclosporine A treatment elicited a significant depletion in liver GSH content and a decrease in the GSH/GSSG ratio that was unrelated to either the time of treatment or the dose used; these effects were already evident after I week of treatment. Renal GSH levels remained unaffected or increased, while those of GSSG increased markedly in all CsA-treated rats, leading to decreases in the GSH/GSSG ratio, except in rats treated in the short term with the lower dose of CsA. These changes in the GSH/GSSG ratio were time and dose dependent. Short-term CsA treatment using the higher dose and long-term treatment with both doses of CsA progressively enhanced lipid peroxidation, which was reflected by increased levels of thiobarbituric acid-reactive substances in both hepatic and renal homogenates. Hepatic γ-glutamylcysteine synthetase activity was increased after long-term treatment with both doses of CsA, whereas the activity of GSH hepatic peroxidase and GSH transferase was not significantly modified in any of the experimental groups. In contrast, renal γ-glutamyl transpeptidase activity decreased in a progressive fashion, with the magnitude of this decrease being dose and time dependent. The plasma levels of total glutathione increased only in rats treated in the long term, regardless of the dose of CsA used, and remained unaltered in animals treated in the short term. 4. In summary, the data collected indicate that CsA treatment alters the interorgan homeostasis of glutathione and the oxidative status of the rat liver and kidney, which is associated with increases in lipid peroxidation in both organs, and also induces modifications in the activity of some enzyme related to the glutathione cycle.Wiley202320232008info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10366/153875reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1538752026-06-07T06:28:51Z
dc.title.none.fl_str_mv Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
title Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
spellingShingle Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
Jiménez Fernández, Rafael
Tratamiento
Metabolismo
Investigación clínica
Medicamentos
Lipid peroxidation
Oxidative stress
Cyclosporine A
Glutathione
Metabolism
Cyclosporine
Glutathione
3209 Farmacología
glutatión
ciclosporina
metabolismo
title_short Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
title_full Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
title_fullStr Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
title_full_unstemmed Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
title_sort Glutathione Metabolism In Cyclosporine A‐Treated Rats: Dose‐ And Time‐Related Changes In Liver And Kidney
dc.creator.none.fl_str_mv Jiménez Fernández, Rafael
Galán Hernández, Ana Isabel
González de Buitrago Arriero, José Manuel
Palomero Labajos, Jesús
Muñoz Bermejo, María Eugenia
author Jiménez Fernández, Rafael
author_facet Jiménez Fernández, Rafael
Galán Hernández, Ana Isabel
González de Buitrago Arriero, José Manuel
Palomero Labajos, Jesús
Muñoz Bermejo, María Eugenia
author_role author
author2 Galán Hernández, Ana Isabel
González de Buitrago Arriero, José Manuel
Palomero Labajos, Jesús
Muñoz Bermejo, María Eugenia
author2_role author
author
author
author
dc.subject.none.fl_str_mv Tratamiento
Metabolismo
Investigación clínica
Medicamentos
Lipid peroxidation
Oxidative stress
Cyclosporine A
Glutathione
Metabolism
Cyclosporine
Glutathione
3209 Farmacología
glutatión
ciclosporina
metabolismo
topic Tratamiento
Metabolismo
Investigación clínica
Medicamentos
Lipid peroxidation
Oxidative stress
Cyclosporine A
Glutathione
Metabolism
Cyclosporine
Glutathione
3209 Farmacología
glutatión
ciclosporina
metabolismo
description [EN] 1. We investigated the simultaneous effects of cyclosporine A (CsA) treatment in rats on glutathione metabolism, oxidative status and their interorgan relationship in the liver and kidney. 2. Reduced and oxidized glutathione (GSH and GSSG, respectively), lipid peroxidation and the activity of several enzymes of the glutathione cycle were evaluated in adult Wistar rats treated daily (i.p.) with saline, CsA vehicle (olive oil) or CsA (10 and 20 mg/kg per day) for either 1 or 4 weeks (short- and long-term treatments, respectively). 3. Cyclosporine A treatment elicited a significant depletion in liver GSH content and a decrease in the GSH/GSSG ratio that was unrelated to either the time of treatment or the dose used; these effects were already evident after I week of treatment. Renal GSH levels remained unaffected or increased, while those of GSSG increased markedly in all CsA-treated rats, leading to decreases in the GSH/GSSG ratio, except in rats treated in the short term with the lower dose of CsA. These changes in the GSH/GSSG ratio were time and dose dependent. Short-term CsA treatment using the higher dose and long-term treatment with both doses of CsA progressively enhanced lipid peroxidation, which was reflected by increased levels of thiobarbituric acid-reactive substances in both hepatic and renal homogenates. Hepatic γ-glutamylcysteine synthetase activity was increased after long-term treatment with both doses of CsA, whereas the activity of GSH hepatic peroxidase and GSH transferase was not significantly modified in any of the experimental groups. In contrast, renal γ-glutamyl transpeptidase activity decreased in a progressive fashion, with the magnitude of this decrease being dose and time dependent. The plasma levels of total glutathione increased only in rats treated in the long term, regardless of the dose of CsA used, and remained unaltered in animals treated in the short term. 4. In summary, the data collected indicate that CsA treatment alters the interorgan homeostasis of glutathione and the oxidative status of the rat liver and kidney, which is associated with increases in lipid peroxidation in both organs, and also induces modifications in the activity of some enzyme related to the glutathione cycle.
publishDate 2008
dc.date.none.fl_str_mv 2008
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/153875
url http://hdl.handle.net/10366/153875
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301629

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