Summary of Study ST001841

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001162. The data can be accessed directly via it's Project DOI: 10.21228/M8H992 This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001841
Study TitleMetabolomics of lung microdissections reveals region- and sex-specific metabolic effects of acute naphthalene exposure in mice (part II)
Study SummaryNaphthalene is a ubiquitous environmental contaminant produced by combustion of fossil fuels and is a primary constituent of both mainstream and side stream tobacco smoke. Naphthalene elicits region-specific toxicity in airway club cells through cytochrome P450 (P450)-mediated bioactivation, resulting in depletion of glutathione and subsequent cytotoxicity. While effects of naphthalene in mice have been extensively studied, few experiments have characterized global metabolomic changes in the lung. In individual lung regions, we found metabolomic changes in microdissected mouse lung conducting airways and parenchyma obtained from animals sacrificed 2, 6, and 24 hours following naphthalene treatment. Data on 577 unique identified metabolites were acquired by accurate mass spectrometry-based assays focusing on lipidomics and non-targeted metabolomics of hydrophilic compounds. Statistical analyses revealed distinct metabolite profiles between the two major lung regions. In addition, the number and magnitude of statistically significant exposure-induced changes in metabolite abundance were different between lung airways and parenchyma for unsaturated lysophosphatidylcholines (LPCs), dipeptides, purines, pyrimidines, and amino acids. Importantly, temporal changes were found to be highly distinct for male and female mice, with males exhibiting predominant treatment-specific changes only at two hours post-exposure. In females, metabolomic changes persisted until six hours post-naphthalene treatment, which may explain the previously characterized higher susceptibility of female mice to naphthalene toxicity. In both males and females, treatment-specific changes corresponding to lung remodeling, oxidative stress response, and DNA damage were observed, which may provide insights into potential mechanisms contributing to the previously reported effects of naphthalene exposure in the lung.
Institute
University of California, Davis
DepartmentGenome Center
LaboratoryFiehn Lab
Last NameStevens
First NameNathanial C.
Address451 Health Sciences Drive University of California Davis Davis, CA 95616
Emailncstevens@ucdavis.edu
Phone828-284-4315
Submit Date2021-06-17
Raw Data AvailableYes
Raw Data File Type(s)raw
Analysis Type DetailGC-MS
Release Date2021-07-05
Release Version1
Nathanial C. Stevens Nathanial C. Stevens
https://dx.doi.org/10.21228/M8H992
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN002984
Analysis type MS
Chromatography type HILIC
Chromatography system Agilent 6550
Column Waters Acquity BEH Amide (150 x 2.1mm,1.7um)
MS Type EI
MS instrument type HILIC
MS instrument name Agilent 6550 QTOF
Ion Mode UNSPECIFIED
Units normalized peak height

MS:

MS ID:MS002774
Analysis ID:AN002984
Instrument Name:Agilent 6550 QTOF
Instrument Type:HILIC
MS Type:EI
MS Comments:LC/MS parameters The LC/QTOFMS analyses are performed using an Agilent 1290 Infinity LC system (G4220A binary pump, G4226A autosampler, and G1316C Column Thermostat). Polar compounds are separated on an Acquity UPLC BEH Amide Column, 130Å, 1.7 µm, 2.1 mm X 150 mm maintained at 45°C at a flow-rate of 0.4 mL/min. Solvent pre-heating (Agilent G1316) was used. The mobile phases consist of: Water, 10 mM Ammonium Formate, 0.125% Formic Acid (A) and Acetonitrile: Water (95/5, v/v), 10 mM Ammonium Formate, 0.125% Formic Acid (B) The gradient is as follows: 0 min 100% (A); 0–2 min 100% (A); 2–7.7 min 30% (A); 7.7–9.5 min 60% (A); 9.5–10.3 min 70% (A); 10.3–12.8 min 0% (A); 12.8–16.8 min 0% (A. A sample volume of 1 µL for positive mode and 3 µL for negative mode is used for the injection. Sample temperature is maintained at 4°C in the autosampler. spectrometers are operated with electrospray ionization (ESI) performing full scan in the mass range m/z 50–1200. Number of cycles in MS1 is 1667 with cycle time of 500ms and accumulation time 475ms. Mass spectrometer parameters are as follows (positive mode) Gas Temp 300°C, gas pressures in psi units with : GS1 and GS2 50 psi, CUR: 35. ISVF is 4500V and DP and CE are 10V and 100 V.
Ion Mode:UNSPECIFIED
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