RT Journal Article
T1 Lipidomics Reveals Cisplatin-Induced Renal Lipid Alterations during Acute Kidney Injury and Their Attenuation by Cilastatin
A1 Moreno Gordaliza, María Estefanía
A1 Marazuela Lamata, María Dolores
A1 Pastor, Óscar
A1 Lázaro Fernández, Alberto
A1 Gómez Gómez, María Milagros
AB 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.
PB MPDI
SN 1422-0067
YR 2021
FD 2021-11-20
LK https://hdl.handle.net/20.500.14352/4835
UL https://hdl.handle.net/20.500.14352/4835
LA eng
NO Ministerio de Economía, Industria y Competitividad (MINECO)
NO Instituto de Salud Carlos III (ISCIII)/FEDER
NO Comunidad de Madrid
NO Insituto de Salud Carlos III (ISCIII)
DS Docta Complutense
RD 3 abr 2025