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

Lookup NU author(s): Professor Peter Thelwall

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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-C-13]-thiazolidine-4-carboxylate, C-13-OTZ) and tracked its uptake and metabolism in vivo in rat brain by C-13 magnetic resonance spectroscopy. Although uptake and clearance of C-13-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 C-13-OTZ over 20 h, however, resulted in C-13-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.

Publication metadata

Author(s): Gamcsik M, Clark MD, Ludeman SM, Springer JB, D'Alessandro MA, Simpson NE, Pourdeyhimi R, Johnson CB, Teeter SD, Blackband SJ, Thelwall PE

Publication type: Article

Publication status: Published

Journal: Neurochemical Research

Year: 2011

Volume: 36

Issue: 3

Pages: 443-451

Print publication date: 01/03/2011

ISSN (print): 0364-3190

ISSN (electronic): 1573-6903

Publisher: Springer New York LLC

URL: http://dx.doi.org/10.1007/s11064-010-0362-5

DOI: 10.1007/s11064-010-0362-5

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