Early detection of unilateral ureteral obstruction by desorption electrospray ionization mass spectrometry

Abstract

Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging analytical tool for rapid in situ assessment of metabolomic profiles on tissue sections without tissue pretreatment or labeling. We applied DESI-MS to identify candidate metabolic biomarkers associated with kidney injury at the early stage. DESI-MS was performed on sections of kidneys from 80 mice over a time course following unilateral ureteral obstruction (UUO) and compared to sham controls. A predictive model of renal damage was constructed using the LASSO (least absolute shrinkage and selection operator) method. Levels of lipid and small metabolites were significantly altered and glycerophospholipids comprised a significant fraction of altered species. These changes correlate with altered expression of lipid metabolic genes, with most genes showing decreased expression. However, rapid upregulation of PG(22:6/22:6) level appeared to be a hitherto unknown feature of the metabolic shift observed in UUO. Using LASSO and SAM (significance analysis of microarrays), we identified a set of well-measured metabolites that accurately predicted UUO-induced renal damage that was detectable by 12 h after UUO, prior to apparent histological changes. Thus, DESI-MS could serve as a useful adjunct to histology in identifying renal damage and demonstrates early and broad changes in membrane associated lipids.

Reversing Hypoxia with PLGA-Encapsulated Manganese Dioxide Nanoparticles Improves Natural Killer Cell Response to Tumor Spheroids

“…The metabolic consequence of hypoxia reduction in the spheroids was analyzed by electrospray ionization mass spectrometry (ESI-MS), a relatively new technique for evaluating metabolic changes in tissues. , In these experiments, spheroids were incubated with different concentrations of PLGA-MnO 2 NPs for 24 h and metabolites were extracted with a mixture of methanol and dichloromethane before analysis by ESI-MS (Figure B). Several metabolites change in abundance with the increasing concentration of PLGA-MnO 2 NP.…”

Expression Profiles of Kidney Mitochondrial Proteome during the Progression of the Unilateral Ureteral Obstruction: Focus on Energy Metabolism Adaptions

“…Complex II belongs to the OXPHOS system and also is part of the TCA cycle catalyzing the transformation of succinate to fumarate and, as a byproduct, producing the electron donor FADH 2 ; therefore, in case of complex I dysfunction, as occurs in the UUO, complex II is able to feed the ETS to maintain OXPHOS. However, more in–depth studies are necessary for evaluating its function during the UUO since some findings also suggest that it could be affected at the first day of the UUO in mice due to the succinate accumulation in renal tissue [ 43 ].…”

Microbial Metabolites in Colorectal Cancer: Basic and Clinical Implications

“…In recent years, advanced analytic platforms including desorption electrospray ionization mass spectrometry (DESI-MS) [ 31 , 32 ], matrix-assisted laser desorption ionization imaging mass spectrometry (MALDI-MS) [ 33 ] and nanoscale secondary ion mass spectrometry (NanoSI-MS) [ 34 ] have been developed to comprehensively enhance the resolution and metabolites coverage of conventional MS-based method. In addition, with the development of machine learning and artificial interagency, advances in computational methods have greatly assisted metabolomics data processing, metabolite identification, as well as in metabolic phenotyping and biomarker discovery [ 35 , 36 ].…”