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Mass spectrometric imaging of metabolites in kidney tissues from rats treated with furosemide
Author(s) -
Choi HyoJung,
Park EuiJung,
Kim Dasom,
Lee YuJung,
Kwon TaeHwan
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1221.3
Subject(s) - furosemide , betaine , carnitine , chemistry , choline , kidney , endocrinology , medicine , urine , acetylcarnitine , mass spectrometry imaging , chromatography , mass spectrometry , biochemistry , organic chemistry
In the kidney, metabolic processes are different among the cortex (COR), outer medulla (OM), and inner medulla (IM). Using a novel technology of the matrix‐assisted laser desorption/ionization (MALDI) and imaging mass spectrometry (IMS), we examined the regional differences of the metabolites in the kidneys of furosemide‐infused rats. Osmotic minipumps were implanted in male Sprague‐Dawley rats to deliver 12 mg/d/rat of furosemide. Vehicle‐treated‐ (n = 14) and furosemide‐treated‐ (furosemide rats, n = 15) rats in metabolic cages received a fixed amount of rat chow (15 g/220 g bw/day/rat) with free access to water intake for 6 days. At day 6, higher urine output (32 ± 4 vs. 9 ± 1 ml/day) and lower urine osmolality (546 ± 44 vs. 1,677 ± 104 mOsm/KgH 2 O) were observed in furosemide rats. Extracts of COR, OM, and IM were analyzed by UPLC/Q‐TOF‐MS, where multivariate analysis revealed significant differences between the two groups. Several metabolites, including acetyl carnitine, betaine, carnitine, choline, and glycerophosphorylcholine (GPC), were significantly changed. The changes of metabolites were further identified by MALDI‐TOF/TOF and IMS. Importantly, their spatial distribution and relative quantitation in the kidneys were analyzed by IMS. Choline compounds were increased in COR and OM, but decreased in IM from furosemide rats. Carnitine compounds were increased in COR and IM, whereas carnitine and acetyl carnitine were decreased in OM. Betaine and GPC were decreased in OM and IM. Taken together, MALDI‐TOF/TOF and IMS successfully provide the spatial distribution and relative quantitation of metabolites in the kidney. Support or Funding Information This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning, Korea (2013R1A1A2007266, and 2014R1A5A2009242).