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Glutathione Articles - Neurodegenerative Diseases
Liposomal-Glutathione Provides Maintenance of Intracellular Glutathione
and Neuroprotection in Mesencephalic Neuronal Cells
Zeevalk GD, Bernard LP, Guilford FT
Neurochemical Research. 2010;35(10):1575–1587
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ABSTRACT
A liposomal preparation of
glutathione (GSH) was investigated for its ability to replenish
intracellular GSH and provide neuroprotection in an in vitro model of
Parkinson’s disease using paraquat plus maneb (PQMB) in rat mesencephalic
cultures. In mixed neuronal/glial cultures depleted of intracellular GSH,
repletion to control levels occurred over 4 h with liposomal-GSH or
nonliposomal-GSH however, liposomal-GSH was 100-fold
more potent; EC50s 4.75 lM and 533 lM for liposomal and non-liposomal-GSH,
respectively. Liposomal-GSH utilization was also observed in neuronal
cultures, but with a higher EC50 (76.5 lM), suggesting that glia facilitate
utilization. Blocking c-glutamylcysteine synthetase with buthionine
sulfoxamine prevented replenishment with liposomal-GSH demonstrating the
requirement for catabolism and resynthesis. Repletion was significantly
attenuated
with endosomal inhibition implicating the endosomal system in utilization.
Liposomal-GSH provided dosedependent protection against PQMB with an EC50
similar to that found for repletion. PQMB depleted intracellular GSH by 50%.
Liposomal-GSH spared endogenous GSH during PQMB exposure, but did not
require GSH biosynthesis for protection. No toxicity was observed with the
liposomal preparation at 200-fold the EC50 for repletion. These findings
indicate that glutathione supplied in a liposomal formulation holds promise
as a potential therapeutic for neuronal maintenance.
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