Summary of Study ST000314

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 PR000253. The data can be accessed directly via it's Project DOI: 10.21228/M8302K This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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Study IDST000314
Study TitleNSAID treatment alters the metabolomics profile of liver, kidney, lung, and heart in an experimental mouse model of heat stroke
Study TypeMetabolomics
Study SummaryThe objective of this study is to exploit broad spectrum metabolomic analysis to identify new biomarkers of multi-organ damage that will improve heat stroke (HS) diagnosis and treatment. The central hypothesis is that HS will lead to significant alterations in multi-organ metabolomics profiles that will serve as markers of HS severity, which will be shifted and intensified further by the acute use of NSAIDs. To test this hypothesis, we will be performing broad spectrum metabolomics to identify alternations in the metabolic signatures of key organs (heart, liver, kidney, and lung) in a highly validated rodent HS model leveraging implantable radiotelemetry. We will then compare these results with already completed histological gene/protein expression analysis to determine the best metabolic markers of HS induced organ damage. The results from this study will aid in the identification of preventative measures to reduce HS risk, as well as in developing therapeutics to treat multi-organ damage and facilitate recovery. The proposed study will provide the first metabolic assessment of HS severity and NSAID use, which will support future studies in HS patients to validate novel biomarkers that will improve clinical assessment of organ damage and recovery.
Institute
University of North Carolina
DepartmentSystems and Translational Sciences
LaboratorySumner Lab
Last NameSumner
First NameSusan
AddressEastern Regional Comprehensive Metabolomics Resource Core, UNC Nutrition Research Institute, 500 Laureate Way, Kannapolis, NC, 28081
Emailsusan_sumner @unc.edu
Phone704-250-5066
Submit Date2015-12-31
Num Groups83
Raw Data AvailableYes
Raw Data File Type(s)fid
Analysis Type DetailNMR
Release Date2016-12-31
Release Version1
Susan Sumner Susan Sumner
https://dx.doi.org/10.21228/M8302K
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000253
Project DOI:doi: 10.21228/M8302K
Project Title:NSAID treatment alters the metabolomics profile of liver, kidney, lung, and heart in an experimental mouse model of heat stroke
Project Summary:Heat stroke (HS) is a significant medical threat to civilians and those serving in the U.S. Armed forces. The physiological and molecular mechanisms that are critical in HS morbidity and mortality, both during and after HS onset, remain yet to be elucidated. Current clinical biomarkers lack specificity and sensitivity to accurately diagnose HS severity, and there is a critical need for effective pharmacologic interventions and treatments that address this life-threatening disease. The systemic inflammatory response (SIR) is one target for such pharmacological interventions, as it is thought to mediate much of HS etiology. For this reason, anti-inflammatories have been directed at the SIR in an effort to treat and prevent HS. Due to their anti-inflammatory actions, non-steroidal anti-inflammatory drugs (NSAIDS) have been suggested as a treatment candidate for HS. Currently, NSAIDs are one of the most widely used medications across the world, with hundreds of millions of doses prescribed yearly. Of special concern, NSAID use is prolific throughout the U.S. Armed Forces. We recently examin4ed the effect of using NSAIDs to treat HS, and found that NSAIDs actually increase HS mortality and exacerbate the systemic organ damage (e.g., gut, kidneys) found in HS recovery in mice. Our finding suggest the use of NSAIDs by civilians and military populations may increase the risk of HS morbidity and mortality. The objective of this proposal is to exploit broad spectrum metabolomic analysis to identify new biomarkers of multi-organ damage that will improve HS diagnosis and treatment.
Institute:US Army Research Institute
Department:Environmental Medicine
Last Name:Audet;Leon
First Name:Gerald;Lisa
Address:Building 42, Kansas Street, Natick, MA 01760
Email:gerald.n.audet.ctr@mail.mil
Phone:508.233.5959

Subject:

Subject ID:SU000334
Subject Type:Animal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57/BL-6
Gender:Male
Species Group:Mammal

Factors:

Subject type: Animal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id heat_group time drug_group
SA014099L_CTRL_POOL_1Control Pool N/A N/A
SA014100L_CTRL_POOL_3Control Pool N/A N/A
SA014101L_CTRL_POOL_2Control Pool N/A N/A
SA014102L_12_084Control 1d 125 ug INDO
SA014103L_12_238Control 1d 125 ug INDO
SA014104L_12_220Control 1d 125 ug INDO
SA014105L_12_281Control 1d 125 ug INDO
SA014106L_12_259Control 1d 125 ug INDO
SA014107L_12_070Control 1d 125 ug INDO
SA014108L_12_076Control 1d 125 ug INDO
SA014109L_12_065Control 1d 125 ug INDO
SA014110L_12_064Control 1d 125 ug INDO
SA014111L_12_285Control 1d No Drug
SA014112L_12_250Control 1d No Drug
SA014113L_12_249Control 1d No Drug
SA014114L_10_299Control 1d No Drug
SA014115L_12_078Control 1d No Drug
SA014116L_12_072Control 1d No Drug
SA014117L_11_422Control 1d No Drug
SA014118L_12_075Control 1d No Drug
SA014119L_10_304Control 1d No Drug
SA014120L_12_280Control T2 125 ug INDO
SA014121L_12_221Control T2 125 ug INDO
SA014122L_12_275Control T2 125 ug INDO
SA014123L_12_317Control T2 125 ug INDO
SA014124L_12_319Control T2 125 ug INDO
SA014125L_12_267Control T2 125 ug INDO
SA014126L_12_318Control T2 125 ug INDO
SA014127L_12_289Control T2 125 ug INDO
SA014128L_12_292Control T2 125 ug INDO
SA014129L_12_272Control T2 No Drug
SA014130L_12_316Control T2 No Drug
SA014131L_12_271Control T2 No Drug
SA014132L_12_295Control T2 No Drug
SA014133L_12_276Control T2 No Drug
SA014134L_12_283Control T2 No Drug
SA014135L_12_265Control T2 No Drug
SA014136L_13_092Control T3b 125 ug INDO
SA014137L_13_076Control T3b 125 ug INDO
SA014138L_13_075Control T3b 125 ug INDO
SA014139L_12_298Control T3b 125 ug INDO
SA014140L_13_110Control T3b 125 ug INDO
SA014141L_13_140Control T3b 125 ug INDO
SA014142L_13_139Control T3b No Drug
SA014143L_13_069Control T3b No Drug
SA014144L_13_100Control T3b No Drug
SA014145L_HS_POOL_3Heat Stroke Pool N/A N/A
SA014146L_HS_POOL_2Heat Stroke Pool N/A N/A
SA014147L_HS_POOL_1Heat Stroke Pool N/A N/A
SA014148L_12_067Heat Stroke 1d 125 ug INDO
SA014149L_12_269Heat Stroke 1d 125 ug INDO
SA014150L_12_234Heat Stroke 1d 125 ug INDO
SA014151L_12_062Heat Stroke 1d 125 ug INDO
SA014152L_12_258Heat Stroke 1d 125 ug INDO
SA014153L_12_079Heat Stroke 1d 125 ug INDO
SA014154L_12_069Heat Stroke 1d No Drug
SA014155L_11_424Heat Stroke 1d No Drug
SA014156L_10_303Heat Stroke 1d No Drug
SA014157L_10_300Heat Stroke 1d No Drug
SA014158L_12_071Heat Stroke 1d No Drug
SA014159L_12_218Heat Stroke 1d No Drug
SA014160L_12_290Heat Stroke 1d No Drug
SA014161L_12_255Heat Stroke 1d No Drug
SA014162L_12_256Heat Stroke 1d No Drug
SA014163L_12_268Heat Stroke T2 125 ug INDO
SA014164L_12_310Heat Stroke T2 125 ug INDO
SA014165L_12_296Heat Stroke T2 125 ug INDO
SA014166L_12_287Heat Stroke T2 125 ug INDO
SA014167L_12_230Heat Stroke T2 125 ug INDO
SA014168L_12_307Heat Stroke T2 125 ug INDO
SA014169L_12_311Heat Stroke T2 125 ug INDO
SA014170L_12_322Heat Stroke T2 125 ug INDO
SA014171L_12_305Heat Stroke T2 125 ug INDO
SA014172L_12_264Heat Stroke T2 No Drug
SA014173L_12_309Heat Stroke T2 No Drug
SA014174L_12_278Heat Stroke T2 No Drug
SA014175L_12_266Heat Stroke T2 No Drug
SA014176L_12_273Heat Stroke T2 No Drug
SA014177L_12_293Heat Stroke T2 No Drug
SA014178L_12_270Heat Stroke T2 No Drug
SA014179L_12_291Heat Stroke T2 No Drug
SA014180L_12_300Heat Stroke T3b 125 ug INDO
SA014181L_13_067Heat Stroke T3b 125 ug INDO
SA014182L_13_115Heat Stroke T3b 125 ug INDO
SA014183L_13_071Heat Stroke T3b 125 ug INDO
SA014184L_13_137Heat Stroke T3b 125 ug INDO
SA014185L_13_093Heat Stroke T3b No Drug
SA014186L_13_066Heat Stroke T3b No Drug
SA014187L_13_134Heat Stroke T3b No Drug
SA014188L_TOT_POOL_3Total Pool N/A N/A
SA014189L_TOT_POOL_2Total Pool N/A N/A
SA014190L_TOT_POOL_1Total Pool N/A N/A
Showing results 1 to 92 of 92

Collection:

Collection ID:CO000328
Collection Summary:-
Sample Type:liver tissue
Storage Conditions:-70C

Treatment:

Treatment ID:TR000348
Treatment Summary:Mouse heat stroke model accurately simulates the thermoregulatory, inflammatory, and organ damage responses observed in HS patients. Mice were Surgically implanted with radiotelemetry devices for the continual recording of core temperatrue during heat expsoure and 24 hours of HS recorvery. Mice were orally trated with vehicle and no drug (bacon-flavored treat) or indomethacin (5 mg/kg contained in a bacon-flavored treat) immediately prior to expsoure to a heated chamger (Model 3950, Therma Forma, Marietta, OH; ambient temperature; = 39.5 degrees celsius). Mice remained in the heated chamber, in the absence of food and water, until a maximum of 42.4 degrees celsius was reached. At the maximum temperature mice were removed from the heat and either sacrificed or provided ad libitum food and water until sacrifice at ~3 hours (when mice displayed maximum hypothermia depth; ~30 degrees C) or 24 hours of recovery (24 hrs after the start of heat exposure) when ~1.0 C fever was displayed. Heart, liver, lung, and kidney were rapidly excised, sliced into transverse or longitudinal sections, and fixed in 10% neutral-buffered formalin for histological analysis (Carson Millonig Formulation, Fisher Scientific, Springfield, MA) or stored at -80 degrees celcius for molecular and metabolomics analysis.
Treatment Protocol ID:USARIEM Protocol A1002 - NSAIDS (INDO)
Treatment Compound:Indomethacin
Treatment Route:Oral
Treatment Dose:5 mg/kg
Treatment Vehicle:Bacon-flavored treat
Animal Endp Tissue Coll List:Heart, Liver, lungs and Kidneys

Sample Preparation:

Sampleprep ID:SP000342
Sampleprep Summary:Aliquots of liver sample were shipped to the NIH RTI-RCMRC on dry ice and immediately stored at -70 °C after being logged in for metabolomics analysis. Frozen tissue samples were transferred to labeled tubes containing stainless steel homogenization beads on dry ice to confirm weights. A total of 83 study samples were thawed on ice for sample preparation. Total tissue contents were extracted during homogenization with a 50:50 acetonitrile:water solution, to generate 2.0-2.5 mg/µl sample homogenates. Samples were centrifuged and an 80 mg equivalent volume (400/320 µl) of homogenized liver supernatants were transferred to new 2.0 mL tubes for the experimental samples. Analytical quality control (QC) phenotypic pool samples were generated by transferring a 50/40 µL aliquot of each supernatant from each respective phenotypic group based on HS-exposure or Controls into different 5 mL tubes. The two phenotypic QC pooled samples were vortexed to mix and a total study QC pool was generated by transferring 650 µL aliquots of each phenotypic pool sample into a new 5 mL tube for mixing. All pooled samples were aliquoted into labeled 2.0 mL tubes like the experimental samples, three for each QC group for an additional 9 samples. The samples were frozen for 2 hr at -70 °C and lyophilized to dryness overnight. Samples were reconstituted in 700 µl of D2O master mix containing 0.2 M Phosphate buffer, pH 7.4 + Chenomx ISTD with 6 mM Imidazole, 9:1 v/v. The tubes were vortexed for 2 min on a multi-tube vortexer and centrifuged at 16,000 rcf for 4 min. A 600 µl aliquot of the supernatant was transferred into pre-labeled 5 mm (4”) NMR tubes for data acquisition on a 700 MHz spectrometer.

Analysis:

Analysis ID:AN000500
Laboratory Name:David H. Murdock Research Institute.
Analysis Type:NMR
Software Version:TopSpin 3.2
Operator Name:Kevin Knagge
Data Format:fid, 1r
Num Factors:15

NMR:

NMR ID:NM000062
Analysis ID:AN000500
Instrument Name:Bruker
Instrument Type:FT-NMR
NMR Experiment Type:Other
Field Frequency Lock:Deuterium
Standard Concentration:0.5 mM
Spectrometer Frequency:700 MHz
NMR Probe:5 mm ATMA Cryoprobe
NMR Solvent:D2O
NMR Tube Size:5mm, 4 inch
Shimming Method:Topshim
Pulse Sequence:noesypr1d
Water Suppression:yes
Receiver Gain:4.5
Offset Frequency:3299.5
Chemical Shift Ref Cpd:DSS
Temperature:298.1 K
Number Of Scans:128
Dummy Scans:4
Acquisition Time:3.893
Spectral Width:12.0227 ppm, 8.417 Hz
Num Data Points Acquired:65536
Real Data Points:65536
Line Broadening:0.5 Hz
Zero Filling:yes
Apodization:Lorentzian
Baseline Correction Method:Polynomial
Chemical Shift Ref Std:DSS-D6
Binned Increment:0.04
Binned Data Excluded Range:4.755 - 4.855 (water); 7.20 - 7.35 (Imidazole)
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