l-S.R-daurisoline protects cultured hippocampal neurons against glutamate neurotoxicity by reducing nitric oxide production.

To explore mechanisms of l-S.R-daurisoline (DS)-mediated protection of cultured hippocampal neurons from sodium glutamate (Glu) cytotoxicity. Cultured neurons obtained from rat hippocampus were used to examine the protective effect of DS against Glu neurotoxicity. Cell viability was estimated using trypan blue dye exclusion method and [3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. Release of nitric oxide (NO) from the hippocampus was assayed using rat thoracic aorta in vitro. DS 0.01-10 mumol.L-1 concentration-dependently inhibited Glu cytotoxicity and increased cell viability with 50% prevention of cell death 2.8 mumol.L-1 (95% confidence limit 1.2-5.9 mumol.L-1). This protection was mostly attenuated by L-arginine (Arg) 1 mmol.L-1. DS 0.01-10 mumol.L-1 did not prevent sodium nitropusside (SNP) 500 mumol.L-1-induced cytotoxicity. DS 10 mumol.L-1 blocked Glu-elicited relaxation of the endothelium-denued rat aortic rings contracted by norepinephrine (NE) 10 mumol.L-1 in the presence of hippocampal tissue, but did not affect that induced by SNP. This indicated that DS inhibited Glu-triggered NO generation but did not prevent the effects of NO. DS prevented neurons from Glu neurotoxicity by inhibiting Glu-triggered NO generation.