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.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST001841 |
| Study Title | Metabolomics of lung microdissections reveals region- and sex-specific metabolic effects of acute naphthalene exposure in mice (part II) |
| Study Summary | Naphthalene 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 |
| Department | Genome Center |
| Laboratory | Fiehn Lab |
| Last Name | Stevens |
| First Name | Nathanial C. |
| Address | 451 Health Sciences Drive University of California Davis Davis, CA 95616 |
| ncstevens@ucdavis.edu | |
| Phone | 828-284-4315 |
| Submit Date | 2021-06-17 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw |
| Analysis Type Detail | GC-MS |
| Release Date | 2021-07-05 |
| Release Version | 1 |
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Project:
| Project ID: | PR001162 |
| Project DOI: | doi: 10.21228/M8H992 |
| Project Title: | Metabolomics of lung microdissections reveals region- and sex-specific metabolic effects of acute naphthalene exposure in mice |
| Project Summary: | Naphthalene 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 |
| Department: | Genome Center |
| Laboratory: | Fiehn Lab |
| Last Name: | Stevens |
| First Name: | Nathanial C. |
| Address: | 451 Health Sciences Drive University of California Davis Davis, CA 95616 |
| Email: | ncstevens@ucdavis.edu |
| Phone: | 828-284-4315 |
| Funding Source: | This study was funded by NIH Grant R01 ES020867, P30 ES023513, and U2C ES030158. During the preparation of this manuscript, Nathanial C. Stevens was supported by Grant Number T32 ES007059. |
| Project Comments: | Study part 1 of 2 |
