Summary of Study ST000575

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 PR000424. The data can be accessed directly via it's Project DOI: 10.21228/M87S4H This work is supported by NIH grant, U2C- DK119886.

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Study IDST000575
Study TitleEffects of the Kinase Inhibitor Sorafenib on Muscle Metabolism In Vivo using Non-targeted Metabolomics Analysis tissue).
Study SummaryThe human kinome consists of ~500 kinases, including 150 proposed as therapeutic targets. progression, cell death, differentiation, and survival. It is not surprising, then, that new tyrosine kinase inhibitors (TKIs) developed to treat cancer also exhibit cardiotoxicity, including sorafenib. We hypothesized that sorafenib cardiotoxicity is related to its deleterious effects on specific cardiac metabolic pathways given the critical role of TKs in cardiac metabolism. FVB/N mice (10/group) were challenged with sorafenib or vehicle control daily for two weeks. Echocardiographic assessment of the heart identified systolic dysfunction consistent with cardiotoxicity compared to vehicle treated controls. Cardiac, skeletal muscle, liver, and serum were flash frozen and prepped for non-targeted GC-MS metabolomics analysis. Compared to vehicle treated controls, sorafenib-treated hearts exhibited significant alterations in 11 metabolites, including markedly altered taurine/hypotaurine metabolism by pathway enrichment analysis (25-fold enrichment). These studies identify sorafenib-induced alterations in cardiac alanine and taurine/hypotaurine metabolic. Interventions to rescue or prevent sorafenib-related cardiotoxicity warrant consideration of therapies targeting the taurine/hypotaurine deficiency identified in the current study.
Institute
University of North Carolina at Chapel Hill
DepartmentMcAllister heart Institute, Department of Internal medicine
LaboratoryMultiple Centers
Last NameWillis
First NameMonte
Address111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA
Emailmonte_willis@med.unc.edu
Phone919-360-7599
Submit Date2017-03-24
Study CommentsHeart, Liver, Skeletal Muscle (Gastrocnemius), Serum
Analysis Type DetailGC-MS
Release Date2018-04-10
Release Version1
Monte Willis Monte Willis
https://dx.doi.org/10.21228/M87S4H
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN000885
Analysis type MS
Chromatography type GC
Chromatography system Agilent 6890N
Column Agilent DB5-MS (15m × 0.25mm, 0.25um)
MS Type EI
MS instrument type Single quadrupole
MS instrument name Agilent 5975
Ion Mode POSITIVE
Units Peak values (Log transformed)

MS:

MS ID:MS000787
Analysis ID:AN000885
Instrument Name:Agilent 5975
Instrument Type:Single quadrupole
MS Type:EI
Ion Mode:POSITIVE
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