[Protective effects of D-3-N-butylphthalide and L-3-N-butylphthalide on neuronal damage induced by KCl and NMDA in cultured rat cortical neurons]

Abstract

The protective effects of l-3-n-butylphthalide (l-NBP) and d-3-n-butylphthalide (d-NBP) on KCl (20 mmol.L-1)- or NMDA (N-methyl-D-aspartate, 30 mumol.L-1)-induced cytotoxicity in primary cultured rat cortical neurons were studied. Intracellular LDH release, percentage of cell death and cellular morphological changes were used to evaluate the effect of drugs. l-NBP (1-100 mumol.L-1) and d-NBP (1-100 mumol.L-1), but not nimodipine (1-100 mumol.L-1), were shown to dose-dependently inhibit LDH release induced by NMDA (30 mumol.L-1) in cultured rat cortical neurons with IC50 values of 4.89 mumol.L-1 and 13.52 mumol.L-1, respectively. The percent cell death was reduced with IC50 values of 44.37 and 49.78 mumol.L-1, and the cellular morphology improved. The effect seemed to be the same as that of equal concentration of NAME(NG-nitro-L-arginine methyl ester). In addition, l-NBP(10 mumol.L-1), d-NBP (10 mumol.L-1) and nimodipine(10 mumol.L-1) also produced significant inhibition on intracellular LDH release and decrease in percent cell death induced by KCl(20 mmol.L-1) in cultured neurons. The potencies of l-NBP and d-NBP were similar to that of equal dose of nimodipine. These data suggest that l-NBP and d-NBP can remarkably protect cultured neurons against the damage induced by KCl and NMDA.