Studies were carried out to investigate the protective effects of pyruvate,
a key glycolytic intermediate and alpha-keto-monocarboxylate, against oxid
ative stress-induced apoptosis. Oxidative stress was induced by treating mo
use thymocytes with 25 mu M hydrogen peroxide for 15 min at 37 degrees C un
der 5% CO2 in air. Pre- and post-treatment of cells with 10 mM pyruvate inh
ibited morphological changes, internucleosomal DNA fragmentation, and trans
location of phosphatidylserine to the plasma membrane surface, which are ch
aracteristic features of apoptosis. L-lactate (10 mM) and acetate (10 mM) w
ere ineffective in inhibiting apoptosis and appeared to be toxic to the cel
ls under similar conditions. The results suggest that pyruvate has therapeu
tic potential for use in the treatment of oxidative stress-induced disorder
s associated with increased apoptosis.