Lipid imaging for visualizing cilastatin amelioration of cisplatin-induced nephrotoxicity



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Moreno Gordaliza, Estefanía and Esteban Fernández, Diego and Lázaro, Alberto and Aboulmagd, Sarah and Humanes, Blanca and Linscheid, Michael W. and Gómez Gómez, M.Milagros (2018) Lipid imaging for visualizing cilastatin amelioration of cisplatin-induced nephrotoxicity. Journal of lipid research, 59 (8). pp. 1561-1574. ISSN 0022-2275

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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.

Item Type:Article
Uncontrolled Keywords:Mass spectrometry, Lipids, Kidney, Cancer, Renal Disease, Molecular Imaging, Cisplatin, Nephroprotection
Subjects:Sciences > Chemistry > Analytic chemistry
ID Code:55250
Deposited On:10 May 2019 10:50
Last Modified:26 Jul 2019 23:01

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