RT Journal Article
T1 Lipid imaging for visualizing cilastatin amelioration of cisplatin-induced nephrotoxicity
A1 Moreno Gordaliza, María Estefanía
A1 Esteban Fernández, Diego
A1 Lázaro Fernández, Alberto
A1 Aboulmagd, Sarah
A1 Humanes, Blanca
A1 Linscheid, Michael W.
A1 Gómez Gómez, María Milagros
AB Nephrotoxicity is a major limitation to cisplatin antitumor therapies. Cilastatin, an inhibitor of renal dehydropeptidase-I, was recently proposed as a promising nephroprotector against cisplatin toxicity, preventing apoptotic cell death. In this work, cilastatin nephroprotection was further investigated in a rat model, with a focus on its effect on 76 renal lipids altered by cisplatin, including 13 new cisplatin-altered mitochondrial cardiolipin species. Lipid imaging was performed with MALDI mass spectrometry imaging (MALDI-MSI) in kidney sections from treated rats. Cilastatin was proved to significantly diminish the lipid distribution alterations caused by cisplatin, lipid levels being almost completely recovered to those of control samples. The extent of recovery of cisplatin-altered lipids by cilastatin turned out to be relevant for discriminating direct or secondary lipid alterations driven by cisplatin. Lipid peroxidation induced by cisplatin was also shown to be reduced when cilastatin was administered. Importantly, significant groups separation was achieved during multivariate analysis of cortex and outer-medullary lipids, indicating that damaged kidney can be discerned from the nephroprotected and healthy groups and classified according to lipid distribution. Therefore, we propose MALDI-MSI as a powerful potential tool offering multimolecule detection possibilities to visualize and evaluate nephrotoxicity and nephroprotection based on lipid analysis.
PB American Society for Biochemistry and Molecular Biology Inc.
SN 0022-2275
YR 2018
FD 2018-07
LK https://hdl.handle.net/20.500.14352/13302
UL https://hdl.handle.net/20.500.14352/13302
LA eng
NO Moreno Gordaliza, E., Esteban Fernández, D., Lázaro Fernández, A. et al. «Lipid Imaging for Visualizing Cilastatin Amelioration of Cisplatin-Induced Nephrotoxicity». Journal of Lipid Research, vol. 59, n.o 9, septiembre de 2018, pp. 1561-74. DOI.org (Crossref), https://doi.org/10.1194/jlr.M080465.
NO Ministerio de Economía, Comercio y Empresa (España)
NO Comunidad de Madrid
NO Instituto de Salud Carlos III/Redes Temáticas de Investigación Cooperativa
DS Docta Complutense
RD 6 abr 2025