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Abstract #2255

Non-Invasive Monitoring of Antioxidant Prodrug Metabolism in Rat Brain by In Vivo 13C MRS

Peter Edward Thelwall1, Daniel Clark2, Susan M. Ludeman3, James B. Springer4, Michael A. D'Alessandro3, Nicholas E. Simpson2, Roxana Pourdeyhimi5, C. Bryce Johnson5, Stephanie D. Teeter5, Stephen J. Blackband2, Michael P. Gamcsik5

1Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, Tyne & Wear, United Kingdom; 2University of Florida; 3Albany College of Pharmacy & Health Sciences; 4Duke University Medical Centre; 5Joint Department of Biomedical Engineering, University of North Carolina / NC State University

Glutathione is an endogenous antioxidant involved in protecting tissues from oxidative stress. Oxidative stress plays a role in some neurodegenerative processes, and therapeutic strategies to combat brain oxidative stress have included raising glutathione concentration. OTZ is a cysteine precursor that can elevate glutathione levels in some tissues. We synthesised 13C-OTZ and tracked its uptake and metabolism in vivo using 13C MRS. The effect of OTZ on brain glutathione content was assessed, and the metabolic fate of 13C-OTZ elucidated from in vivo and ex vivo spectroscopy and mass spectrometry of rat brain.