Summary of Study ST001871
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 PR001181. The data can be accessed directly via it's Project DOI: 10.21228/M82418 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 | ST001871 |
| Study Title | Untargeted LC-MS metabolomics analysis of cecal content of mice treated with TCDD vs. vehicle control (part I) |
| Study Type | Untargeted metabolomics |
| Study Summary | Six-week-old female wildtype (WT) C57BL/6 mice were administered a single 100µl intraperitoneal injection containing sterile corn oil (VEH group) or an intraperitoneal injection of 10µg/kg TCDD suspended within sterile corn oil (TCDD group). At the 72h time point following TCDD or VEH exposure, the mice were humanely euthanized by an overdose of inhaled isoflurane. During necropsy, cecal content and blood serum samples were collected for untargeted metabolomics profiling. |
| Institute | University of South Carolina School of Medicine |
| Department | Department of Pathology |
| Laboratory | (On behalf of) Mitzi Nagarkatti Lab |
| Last Name | Lai |
| First Name | Yunjia |
| Address | 135 Dauer Drive, Chapel Hill, NC 27599 |
| yunjia.lai@outlook.com | |
| Phone | 919-480-5489 |
| Submit Date | 2021-07-16 |
| Num Groups | 2 |
| Total Subjects | 20 |
| Num Females | 20 |
| Publications | Chemosphere |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2021-08-30 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001181 |
| Project DOI: | doi: 10.21228/M82418 |
| Project Title: | Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure on the Circulating and Cecal Metabolome Profile |
| Project Type: | Untargeted metabolomics |
| Project Summary: | 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a polyhalogenated planar hydrocarbon belonging to a group of highly toxic and persistent environmental contaminants known as “dioxins”. TCDD is an animal teratogen and carcinogen that is well characterized for causing immunosuppression through activation of Aryl Hydrocarbon Receptor (AHR). In the current study, we investigated the effect of exposure of mice to an acute dose of TCDD on the metabolic profile within the serum and cecal contents to better define the effects of TCDD on host physiology. Our findings demonstrated that within the circulating metabolome following acute TCDD, there was significant dysregulation in the metabolism of bioactive lipids, amino acids, and carbohydrates when compared to the VEH treated mice. These wide-spread changes in metabolite abundance were identified to regulate host immunity via modulating Nuclear Factor-Kappa B (NF-κB) and Extracellular Signal‑Regulated Protein Kinase (ERK1/2) activity, and work as biomarkers for a variety of organ injuries and dysfunctions that follow TCDD exposure. Within the cecal content, of mice exposed to TCDD, we were able to detect changes in inflammatory markers that regulate NF-κB, markers of injury-related inflammation, and changes in lysine degradation, nicotinamide metabolism, and butanoate metabolism, which suggested an immediate suppression microbial metabolism. Collectively, these results demonstrate that acute TCDD exposure results in immediate irregularities in the circulating and intestinal metabolome which likely contributes to TCDD toxicity and can be used as biomarkers for the early detection of individual exposure. |
| Institute: | University of South Carolina School of Medicine |
| Department: | Department of Pathology |
| Laboratory: | On behalf of Dr. Mitzi Nagarkatti Lab |
| Last Name: | Lai |
| First Name: | Yunjia |
| Address: | 1104 MHRC, 135 Dauer Dr., Chapel Hill, NC, 27599, USA |
| Email: | yunjia.lai@outlook.com |
| Phone: | 9194805489 |
| Funding Source: | National Institute of Health: P01AT003961, P20GM103641, R01ES030144, R01AI129788 and R01AI123947 |
| Project Comments: | This is supporting metabolomics data for the publication in Chemosphere. |
| Publications: | Chemosphere |
Subject:
| Subject ID: | SU001948 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Genotype Strain: | C57BL/6 mice (Wild-type) |
| Age Or Age Range: | six weeks old |
| Gender: | Female |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Experimental factor |
|---|---|---|
| SA174745 | CT5 | TCDD |
| SA174746 | CT4 | TCDD |
| SA174747 | CT3 | TCDD |
| SA174748 | CT6 | TCDD |
| SA174749 | CT8 | TCDD |
| SA174750 | CT10 | TCDD |
| SA174751 | CT9 | TCDD |
| SA174752 | CT2 | TCDD |
| SA174753 | CT7 | TCDD |
| SA174754 | CT1 | TCDD |
| SA174755 | CV5 | Vehicle |
| SA174756 | CV4 | Vehicle |
| SA174757 | CV3 | Vehicle |
| SA174758 | CV2 | Vehicle |
| SA174759 | CV6 | Vehicle |
| SA174760 | CV7 | Vehicle |
| SA174761 | CV10 | Vehicle |
| SA174762 | CV9 | Vehicle |
| SA174763 | CV8 | Vehicle |
| SA174764 | CV1 | Vehicle |
| Showing results 1 to 20 of 20 |
Collection:
| Collection ID: | CO001941 |
| Collection Summary: | Six-week-old female wildtype (WT) C57BL/6 mice acquired from Jackson Laboratories (Bar Harbor, ME) were housed in an AAALAC-accredited specific-pathogen-free animal facility located at the grounds of the University of South Carolina School of Medicine for the entirety of all experiments. Mice within the facility were housed within polycarbonate cages containing cellulose fiber chips as bedding in a temperature and humidity-controlled environment. After a 2-week acclimatization period, the mice were divided randomly into two groups that would be administered a single 100µl intraperitoneal injection containing sterile corn oil (VEH group) or an intraperitoneal injection of 10µg/kg TCDD suspended within sterile corn oil (TCDD group). At the 72h time point following TCDD or VEH exposure, the mice were humanely euthanized by an overdose of inhaled isoflurane. Cecal content and blood sera were collected at the time of necropsy. |
| Sample Type: | Cecal content |
Treatment:
| Treatment ID: | TR001960 |
| Treatment Summary: | Six-week-old female wildtype (WT) C57BL/6 mice acquired from Jackson Laboratories (Bar Harbor, ME) were housed in an AAALAC-accredited specific-pathogen-free animal facility located at the grounds of the University of South Carolina School of Medicine for the entirety of all experiments. Mice within the facility were housed within polycarbonate cages containing cellulose fiber chips as bedding in a temperature and humidity-controlled environment. After a 2-week acclimatization period, the mice were divided randomly into two groups that would be administered a single 100µl intraperitoneal injection containing sterile corn oil (VEH group) or an intraperitoneal injection of 10µg/kg TCDD suspended within sterile corn oil (TCDD group). At the 72h time point following TCDD or VEH exposure, the mice were humanely euthanized by an overdose of inhaled isoflurane. Cecal content and blood sera were collected at the time of necropsy. |
Sample Preparation:
| Sampleprep ID: | SP001954 |
| Sampleprep Summary: | Cecal content and serum samples were processed according to previously described methods for the metabolomic profiling using liquid chromatography-mass spectrometry (LC-MS) with slight modifications. For cecal content, ~25 mg was aliquoted into 1.5-mL Eppendorf tubes (Hamburg, Germany) containing ~20 mg acid washed glass beads (Sigma-Aldrich, St. Louis, MO), extracted into ice-cold MeOH:water (1:1, v/v) on a Qiagen TissueLyzer at 50 Hz for 10 min (Hilden, Germany), and centrifuged at 12,000 rpm for 10 min. For blood sera, 20 µL aliquots were extracted by adding 180 µL cold MeOH, briefly vortexed, and incubated at -20ºC for 30 min for protein precipitation. The supernatants of both matrices were dried in a CentriVap vacuum concentrator (Labconco, MO) and resuspended in ACN:water (2:98, v/v) upon analysis. |
Combined analysis:
| Analysis ID | AN003033 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Thermo Vanquish |
| Column | Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um) |
| MS Type | ESI |
| MS instrument type | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE |
| Units | m/z |
Chromatography:
| Chromatography ID: | CH002246 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Waters Acquity BEH HSS T3 (100 x 2.1mm,1.8um) |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS002820 |
| Analysis ID: | AN003033 |
| Instrument Name: | Thermo Q Exactive Orbitrap |
| Instrument Type: | Orbitrap |
| MS Type: | ESI |
| MS Comments: | fullscan *.raw data acquired by Thermo XCalibur software |
| Ion Mode: | POSITIVE |
