Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin

Nephrotoxicity is a major complication of cisplatin-based chemotherapy, leading to acute kidney injury in ca. 30% of patients, with no preventive intervention or treatment available for clinical use. Cilastatin has proved to exert a nephroprotective effect for cisplatin therapies in in vitro and in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Estefanía Moreno-Gordaliza, Maria Dolores Marazuela, Óscar Pastor, Alberto Lázaro, María Milagros Gómez-Gómez
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	lipidomics cisplatin acute kidney injury cilastatin nephroprotection biomarkers Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/101ae9934e0042989ff7186d0b177d8f
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:101ae9934e0042989ff7186d0b177d8f
record_format	dspace
spelling	oai:doaj.org-article:101ae9934e0042989ff7186d0b177d8f2021-11-25T17:57:29ZLipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin10.3390/ijms2222125211422-00671661-6596https://doaj.org/article/101ae9934e0042989ff7186d0b177d8f2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12521https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Nephrotoxicity is a major complication of cisplatin-based chemotherapy, leading to acute kidney injury in ca. 30% of patients, with no preventive intervention or treatment available for clinical use. Cilastatin has proved to exert a nephroprotective effect for cisplatin therapies in in vitro and in vivo models, having recently entered clinical trials. A deeper understanding at the molecular level of cisplatin-induced renal damage and the effect of potential protective agents could be key to develop successful nephroprotective therapies and to establish new biomarkers of renal damage and nephroprotection. A targeted lipidomics approach, using LC-MS/MS, was employed for the quantification of 108 lipid species (comprising phospholipids, sphingolipids, and free and esterified cholesterol) in kidney cortex and medulla extracts from rats treated with cisplatin and/or cilastatin. Up to 56 and 63 lipid species were found to be altered in the cortex and medulla, respectively, after cisplatin treatment. Co-treatment with cilastatin attenuated many of these lipid changes, either totally or partially with respect to control levels. Multivariate analysis revealed that lipid species can be used to discriminate renal damage and nephroprotection, with cholesterol esters being the most discriminating species, along with sulfatides and phospholipids. Potential diagnostic biomarkers of cisplatin-induced renal damage and cilastatin nephroprotection were also found.Estefanía Moreno-GordalizaMaria Dolores MarazuelaÓscar PastorAlberto LázaroMaría Milagros Gómez-GómezMDPI AGarticlelipidomicscisplatinacute kidney injurycilastatinnephroprotectionbiomarkersBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12521, p 12521 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lipidomics cisplatin acute kidney injury cilastatin nephroprotection biomarkers Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	lipidomics cisplatin acute kidney injury cilastatin nephroprotection biomarkers Biology (General) QH301-705.5 Chemistry QD1-999 Estefanía Moreno-Gordaliza Maria Dolores Marazuela Óscar Pastor Alberto Lázaro María Milagros Gómez-Gómez Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin
description	Nephrotoxicity is a major complication of cisplatin-based chemotherapy, leading to acute kidney injury in ca. 30% of patients, with no preventive intervention or treatment available for clinical use. Cilastatin has proved to exert a nephroprotective effect for cisplatin therapies in in vitro and in vivo models, having recently entered clinical trials. A deeper understanding at the molecular level of cisplatin-induced renal damage and the effect of potential protective agents could be key to develop successful nephroprotective therapies and to establish new biomarkers of renal damage and nephroprotection. A targeted lipidomics approach, using LC-MS/MS, was employed for the quantification of 108 lipid species (comprising phospholipids, sphingolipids, and free and esterified cholesterol) in kidney cortex and medulla extracts from rats treated with cisplatin and/or cilastatin. Up to 56 and 63 lipid species were found to be altered in the cortex and medulla, respectively, after cisplatin treatment. Co-treatment with cilastatin attenuated many of these lipid changes, either totally or partially with respect to control levels. Multivariate analysis revealed that lipid species can be used to discriminate renal damage and nephroprotection, with cholesterol esters being the most discriminating species, along with sulfatides and phospholipids. Potential diagnostic biomarkers of cisplatin-induced renal damage and cilastatin nephroprotection were also found.
format	article
author	Estefanía Moreno-Gordaliza Maria Dolores Marazuela Óscar Pastor Alberto Lázaro María Milagros Gómez-Gómez
author_facet	Estefanía Moreno-Gordaliza Maria Dolores Marazuela Óscar Pastor Alberto Lázaro María Milagros Gómez-Gómez
author_sort	Estefanía Moreno-Gordaliza
title	Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin
title_short	Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin
title_full	Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin
title_fullStr	Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin
title_full_unstemmed	Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin
title_sort	lipidomics reveals cisplatin-induced renal lipid alterations during acute kidney injury and their attenuation by cilastatin
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/101ae9934e0042989ff7186d0b177d8f
work_keys_str_mv	AT estefaniamorenogordaliza lipidomicsrevealscisplatininducedrenallipidalterationsduringacutekidneyinjuryandtheirattenuationbycilastatin AT mariadoloresmarazuela lipidomicsrevealscisplatininducedrenallipidalterationsduringacutekidneyinjuryandtheirattenuationbycilastatin AT oscarpastor lipidomicsrevealscisplatininducedrenallipidalterationsduringacutekidneyinjuryandtheirattenuationbycilastatin AT albertolazaro lipidomicsrevealscisplatininducedrenallipidalterationsduringacutekidneyinjuryandtheirattenuationbycilastatin AT mariamilagrosgomezgomez lipidomicsrevealscisplatininducedrenallipidalterationsduringacutekidneyinjuryandtheirattenuationbycilastatin
_version_	1718411786051387392

Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin

Ejemplares similares