Aim: To explore mechanisms of l-S.R-daurisoline (DS)-mediated protection of cultured hippocampal neurons from sodium glutamate (Glu) cytotoxicity.
Methods: 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.
Results: 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.
Conclusion: DS prevented neurons from Glu neurotoxicity by inhibiting Glu-triggered NO generation.