AIM: To evaluate the effects of L-pyroglutamic acid (L-PGA, L-5-oxo-2-pyrro
lidinecaroxylic acid) on sodium glutamate-induced neurotoxicity in rat cort
ical neurons. METHODS: In primary cortical cultures from 16-d-old fetal rat
, neuronal viability and contents of nitrite in the bathing medium after tr
ansient exposure to sodium glutamate (Glu) were measured; with Fura 2-AM as
an intracellular calcium indicator, AR-CM-MIC cation measurement system wa
s used to examine cytosolic free calcium ([Ca2+](i)). RESULTS: L-PGA 10 - 8
0 mu mol.L-1, inhibited Glu (500 mu mol. L-1)-induced neuronal loss in a co
ncentration dependent manner with IC50 value of (41 +/- 9) mu mol. L-1(95 %
confidence limits: 30.3 - 54.7 mu mol. L-PGA also attenuated Glu-induced N
O release. L-PGA 1, 3, 10, 30, and 100 mu mol.L-1 depressed Glu-caused [Ca2
+](i) elevation by 20.5 %, 34.4 %, 47.7 %, 70.6 %, and 80.4 %, respectively
. CONCLUSION: L-PGA protects cortical neurons against Glu-induced neurotoxi
ty which may be related to inhibition of NO formation or suppression of the
rise in [Ca2+](i).