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|Title:||A novel neuroprotective agent with antioxidant and nitric oxide synthase inhibitory action|
Arthur J. Olson
University of Toyama
Scripps Research Institute
|Keywords:||Biochemistry, Genetics and Molecular Biology|
|Citation:||Free Radical Research. Vol.40, No.7 (2006), 685-695|
|Abstract:||Nα-vanillyl-Nα-nitroarginine (N - 1) that combines the active functions of natural antioxidant and nitric oxide synthase inhibitor was developed for its neuroprotective properties. N - 1 exhibited protective effects against hydrogen peroxide-induced 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 75 μmol/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.|
|Appears in Collections:||Scopus 2006-2010|
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