Neurochemical Research

, Volume 36, Issue 3, pp 443–451 | Cite as

Non-invasive Monitoring of L-2-Oxothiazolidine-4-Carboxylate Metabolism in the Rat Brain by In vivo 13C Magnetic Resonance Spectroscopy

  • Michael P. Gamcsik
  • M. Daniel Clark
  • Susan M. Ludeman
  • James B. Springer
  • Michael A. D’Alessandro
  • Nicholas E. Simpson
  • Roxana Pourdeyhimi
  • C. Bryce Johnson
  • Stephanie D. Teeter
  • Stephen J. Blackband
  • Peter E. Thelwall
Original Paper

Abstract

The cysteine precursor L-2-oxothiazolidine-4-carboxylate (OTZ, procysteine) can raise cysteine concentration, and thus glutathione levels, in some tissues. OTZ has therefore been proposed as a prodrug for combating oxidative stress. We have synthesized stable isotope labeled OTZ (i.e. L-2-oxo-[5-13C]-thiazolidine-4-carboxylate, 13C-OTZ) and tracked its uptake and metabolism in vivo in rat brain by 13C magnetic resonance spectroscopy. Although uptake and clearance of 13C-OTZ was detectable in rat brain following a bolus dose by in vivo spectroscopy, no incorporation of isotope label into brain glutathione was detectable. Continuous infusion of 13C-OTZ over 20 h, however, resulted in 13C-label incorporation into glutathione, taurine, hypotaurine and lactate at levels sufficient for detection by in vivo magnetic resonance spectroscopy. Examination of brain tissue extracts by mass spectrometry confirmed only low levels of isotope incorporation into glutathione in rats treated with a bolus dose and much higher levels after 20 h of continuous infusion. In contrast to some previous studies, bolus administration of OTZ did not alter brain glutathione levels. Even a continuous infusion of OTZ over 20 h failed to raise brain glutathione levels. These studies demonstrate the utility of in vivo magnetic resonance for non-invasive monitoring of antioxidant uptake and metabolism in intact brain. These types of experiments can be used to evaluate the efficacy of various interventions for maintenance of brain glutathione.

Keywords

Magnetic resonance Metabolism Cysteine Glutathione Taurine 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Michael P. Gamcsik
    • 1
  • M. Daniel Clark
    • 2
  • Susan M. Ludeman
    • 3
  • James B. Springer
    • 4
  • Michael A. D’Alessandro
    • 3
  • Nicholas E. Simpson
    • 5
  • Roxana Pourdeyhimi
    • 1
  • C. Bryce Johnson
    • 1
  • Stephanie D. Teeter
    • 1
  • Stephen J. Blackband
    • 2
  • Peter E. Thelwall
    • 6
  1. 1.UNC/NCSU Joint Department of Biomedical EngineeringRaleighUSA
  2. 2.Department of Neuroscience, McKnight Brain InstituteUniversity of FloridaGainesvilleUSA
  3. 3.Departments of Arts and Sciences and Pharmaceutical SciencesAlbany College of Pharmacy and Health SciencesAlbanyUSA
  4. 4.Department of MedicineDuke University Medical CenterDurhamUSA
  5. 5.Department of MedicineUniversity of FloridaGainesvilleUSA
  6. 6.Newcastle Magnetic Resonance Centre, Campus for Ageing and VitalityNewcastle UniversityNewcastle upon TyneUK

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