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Volume 17, Number 23,
Issue of December 1, 1997
pp. 9060-9067
Pyruvate Protects Neurons against Hydrogen Peroxide-Induced
Toxicity
Received June 6, 1997; revised Sept. 17, 1997; accepted Sept. 23, 1997.
Solange Desagher,
Jacques Glowinski, and
Joël Prémont
Chaire de Neuropharmacologie, Institut National de la Santé
et de la Recherche Médicale U114, Collège de France, 75 231 Paris Cedex 05, France
Hydrogen peroxide (H2O2) is
suspected to be involved in numerous brain pathologies such as
neurodegenerative diseases or in acute injury such as ischemia or
trauma. In this study, we examined the ability of pyruvate to improve
the survival of cultured striatal neurons exposed for 30 min to
H2O2, as estimated 24 hr later by the
3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazoliumbromide assay.
Pyruvate strongly protected neurons against both
H2O2 added to the external medium and
H2O2 endogenously produced through the redox
cycling of the experimental quinone menadione. The neuroprotective effect of pyruvate appeared to result rather from the ability of
 -ketoacids to undergo nonenzymatic decarboxylation in the presence
of H2O2 than from an improvement of energy
metabolism. Indeed, several other -ketoacids, including
-ketobutyrate, which is not an energy substrate, reproduced the
neuroprotective effect of pyruvate. In contrast, lactate, a neuronal
energy substrate, did not protect neurons from
H2O2. Optimal neuroprotection was achieved with
relatively low concentrations of pyruvate ( 1 mM), whereas
at high concentration (10 mM) pyruvate was ineffective. This paradox could result from the cytosolic acidification induced by
the cotransport of pyruvate and protons into neurons. Indeed, cytosolic
acidification both enhanced the H2O2-induced
neurotoxicity and decreased the rate of pyruvate decarboxylation by
H2O2. Together, these results indicate that
pyruvate efficiently protects neurons against both exogenous and
endogenous H2O2. Its low toxicity and its
capacity to cross the blood-brain barrier open a new therapeutic perspective in brain pathologies in which H2O2
is involved.
Key words:
pyruvate;
-ketoacids;
antioxidants;
hydrogen peroxide;
menadione;
oxidative stress;
neuroprotection;
neurotoxicity
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