Journal article
Disruption in glutathione metabolism and altered energy production in the liver and kidney after ischemic acute kidney injury in mice
Scientific reports, Vol.14(1), 13862
06/15/2024
DOI: 10.1038/s41598-024-64586-4
PMCID: PMC11180093
PMID: 38879688
Abstract
Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8–10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.
Details
- Title: Subtitle
- Disruption in glutathione metabolism and altered energy production in the liver and kidney after ischemic acute kidney injury in mice
- Creators
- Peter R Baker - University of Colorado Anschutz Medical CampusAmy S Li - University of Colorado Anschutz Medical CampusBenjamin R Griffin - University of IowaHyo-Wook GilDavid J Orlicky - University of Colorado Anschutz Medical CampusBenjamin M Fox - University of Colorado Anschutz Medical CampusBryan Park - University of Colorado Anschutz Medical CampusGenevieve C Sparagna - University of Colorado Anschutz Medical CampusJared GoffChristopher Altmann - University of Colorado Anschutz Medical CampusHanan Elajaili - University of Colorado Anschutz Medical CampusKayo OkamuraZhibin He - University of Colorado Anschutz Medical CampusDaniel Stephenson - University of Colorado Anschutz Medical CampusAngelo D’Alessandro - University of Colorado Anschutz Medical CampusJulie A Reisz - University of Colorado Anschutz Medical CampusEva S Nozik - University of Colorado Anschutz Medical CampusCarmen C Sucharov - University of Colorado Anschutz Medical CampusSarah Faubel - University of Colorado Anschutz Medical Campus
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.14(1), 13862
- Publisher
- Nature Publishing Group
- DOI
- 10.1038/s41598-024-64586-4
- PMID
- 38879688
- PMCID
- PMC11180093
- eISSN
- 2045-2322
- Language
- English
- Date published
- 06/15/2024
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984642759902771
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