Visualization of renal rotenone accumulation after oral administration and in situ detection of kidney injury biomarkers via MALDI mass spectrometry imaging

The examination of drug accumulation within complex biological systems offers valuable insights into the molecular aspects of drug metabolism and toxicity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is an innovative methodology that enables the spatial visualiz...

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Bibliographic Details
Published in:	Frontiers in molecular biosciences Vol. 11; p. 1366278
Main Authors:	Tenebro, Chuckcris P, Marcial, Neaven Bon Joy M, Salcepuedes, Janine J, Torrecampo, Josie C, Hernandez, Rajelle D, Francisco, John Alfon P, Infante, Kristine Mae G, Belardo, Veronica J, Paderes, Monissa C, Alvero, Rita Grace Y, Saludes, Jonel P, Dalisay, Doralyn S
Format:	Journal Article
Language:	English
Published:	Switzerland Frontiers Media S.A 01-07-2024
Subjects:	drug metabolism endogenous metabolite kidney tissues MALDI MSI Molecular Biosciences rotenone toxicity toxicity kidney tissues drug metabolism rotenone MALDI MSI endogenous metabolite anticancer
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Summary:	The examination of drug accumulation within complex biological systems offers valuable insights into the molecular aspects of drug metabolism and toxicity. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is an innovative methodology that enables the spatial visualization and quantification of biomolecules as well as drug and its metabolites in complex biological system. Hence, this method provides valuable insights into the metabolic profile and any molecular changes that may occur as a result of drug treatment. The renal system is particularly vulnerable to adverse effects of drug-induced harm and toxicity. In this study, MALDI MSI was utilized to examine the spatial distribution of drug and renal metabolites within kidney tissues subsequent to a single oral dosage of the anticancer compound rotenone. The integration of ion mobility spectrometry with MALDI MSI enhanced the data acquisition and analysis, resulting to improved mass resolution. Subsequently, the MS/MS fragment ions of rotenone reference drug were detected and characterized using MALDI HDMS/MS imaging. Notably, drug accumulation was observed in the cortical region of the representative kidney tissue sections treated with rotenone. The histological examination of treated kidney tissues did not reveal any observable changes. Differential ion intensity of renal endogenous metabolites was observed between untreated and rotenone-treated tissues. In the context of treated kidney tissues, the ion intensity level of sphingomyelin (D18:1/16:0), a sphingolipid indicator of glomerular cell injury and renal damage, was found to be elevated significantly compared to untreated kidney tissues. Conversely, the ion intensities of choline, glycero-3-phosphocholine (GPC), inosine, and a lysophosphatidylcholine LysoPC(18:0) exhibited a significant decrease. The results of this study demonstrate the potential of MALDI MSI as a novel technique for investigating the spatial distribution of drugs and renal endogenous molecules while preserving the anatomical integrity of the kidney tissue. This technique can be used to study drug-induced metabolism and toxicity in a dynamic manner.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Michael Rehman, Yale University, United States Elizabeth Neumann, University of California, Davis, United States Reviewed by: Vinod Kumar Narayana, The University of Melbourne, Australia Van-An Duong, University of Texas Health Science Center at Houston, United States
ISSN:	2296-889X 2296-889X
DOI:	10.3389/fmolb.2024.1366278