title: MALDI-LTQ-Orbitrap mass spectrometry imaging for lipidomic analysis in kidney under cisplatin chemotherapy.
abstract: Imaging techniques for mapping molecular distributions in tissue sections can reveal valuable information on biomolecules involved in relevant biochemical processes. A method has been developed for comprehensive, reproducible and sensitive lipid imaging by matrix-assisted laser/desorption ionization-LTQ-Orbitrap mass spectrometry in kidney sections, showing the benefits of exact mass determination. Matrix deposition parameters for positive and negative lipid ion imaging using different matrices such as 2,5-dihydroxybenzoic acid (DHB), 9-aminoacridine (9-AA) or α-cyano-4-hydroxycinnamic acid (CHCA) have been optimized for the broadest detection and identification of renal lipids. The combination of 9-AA and DHB was found as the most suitable for negative and positive ion mode lipid imaging, respectively. Lipid mapping and related identification strategies and limitations have also been discussed. Production of 100-µm resolution images was proved to be enough for discerning lipid distribution in kidney substructures. Imaging reproducibility was assessed on parallel kidney slices with time. This method has been applied to the lipidomics analysis on kidney sections from rats treated with the antitumor drug cisplatin and compared to healthy control rats. Up to 66 different renal lipids out of 450 extracted ion images (mainly phospholipid species, in addition to sulfatides and cholesterol sulfate) have been found and identified showing a modified distribution pattern due to cisplatin-induced nephrotoxicity. These lipid species reflect either topographic, signaling or structural processes in damaged kidney and could potentially be used for nephrotoxicity assessment or as therapeutic targets. This is, to our knowledge, the first imaging lipidomics study for nephrotoxicity assessment of cisplatin chemotherapy.
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. Electronic address: emorenog@ucm.es.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Moreno-Gordaliza
authors.affiliation: Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor Str. 2, 12489 Berlin, Germany.
authors.forename: Diego
authors.initials: D
authors.lastname: Esteban-Fernández
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, C/ Dr. Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Lázaro
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, C/ Dr. Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Humanes
authors.affiliation: Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor Str. 2, 12489 Berlin, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Aboulmagd
authors.affiliation: Renal Pathophysiology Laboratory, Department of Nephrology, Instituto de Investigación Sanitaria Gregorio Marañón, Hospital General Universitario Gregorio Marañón, C/ Dr. Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Tejedor
authors.affiliation: Department of Chemistry, Humboldt-Universität zu Berlin, Brook-Taylor Str. 2, 12489 Berlin, Germany.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Linscheid
authors.affiliation: Department of Analytical Chemistry, Faculty of Chemistry, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040 Madrid, Spain.
authors.forename: M Milagros
authors.initials: MM
authors.lastname: Gómez-Gómez
mesh_terms: D000818:Animals; D002945:Cisplatin / Q000009:adverse effects*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D057054:Molecular Imaging; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D002945:Cisplatin
keywords: Cisplatin; Imaging; Kidney; Lipid; MALDI Orbitrap mass spectrometry; Nephrotoxicity