期刊
FREE RADICAL RESEARCH
卷 40, 期 7, 页码 685-695出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10715760500423763
关键词
nitric oxide synthase; neuroprotection; cell culture; NG108-15; microdialysis; nitro arginine
N-alpha-vanillyl-N-omega-nitroarginine (N - 1) that combines the active functions of natural antioxidant and nitric oxide synthase inhibitor was developed for its neuroprotective properties. N - I exhibited protective effects against hydrogen peroxideinduced cell damage and the inhibitory effect on nitric oxide 'NO' production induced by calcium ionophore in NG 108-15 cells. N - 1 inhibited the constitutive NOS isolated from rat cerebellar in a greater extent than constitutive NOS from human endothelial cells. Low binding energy (-10.2 kcal/mol) obtained from docking N - 1 to nNOS supported the additional mode of action of N - 1 as an nNOS inhibitor. The in vivo neuroprotective effect on kainic acid-induced nitric oxide production and neuronal cell death in rat brain was investigated via microdialysis. Rats were injected intra-peritonially with N - 1 at 7 5 mu mol/kg before kainic acid injection (10 mg/kg). The significant suppression effect on kainic acid-induced NO and significant increase in surviving cells were observed in the hippocampus at 40 min after the induction.
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