In Vivo Brain Oxidative Stress Model Induced by Microinjection of Sodium Nitroprusside in Mice

Abstract

Abstract. Sodium nitroprusside (SNP) is widely used as a potent vasodilator and a nitric oxide (NO) donor, whereas the cytotoxicity of SNP has been well documented. SNP releases several potentially toxic products such as cyanide anion, NO, and iron. We investigated the mechanisms of cell death and motor dysfunction induced by microinjection of SNP in mice to establish a brain oxidative stress model and then examined the anti-oxidant activity of glutathione. Intrastriatal microinjection of SNP (1 -10 nmol) induced brain damage and motor dysfunction in a dose-dependent manner when the effects were evaluated with behavioral tests and TTC staining. NOC-18 (10 nmol), another NO donor, and KCN (10 nmol) did not cause motor dysfunction. However, FeCl 2 (10 nmol) caused motor dysfunction. In addition, simultaneous injection of SNP and deferoxamine (10 nmol), an iron-chelating agent, prevented SNP-induced brain damage and motor dysfunction, suggesting a role of iron-related radicals in SNP-toxicity. Moreover, reduced glutathione (1 -10 nmol), a natural anti-oxidant substance, dose-dependently prevented motor dysfunction induced by SNP-toxicity. Finally, deferoxamine and glutathione (10 nmol) significantly protected against brain damage and motor dysfunction induced by FeCl 2 toxicity. These results suggest that cell death induced by injection of SNP is caused by iron-related radical reactions, but not by NO and cyanide anion.

In VivoImaging of Reactive Oxygen Species in Mouse Brain by using [3H]Hydromethidine as a Potential Radical Trapping Radiotracer

“…It has been reported that SNP caused cell death dose-dependently when microinjected into the striatum. 23 In addition, cell death induced by intrastriatal microinjection of SNP was caused by iron-related ROS such as OH…”

Protective Effect of Luteolin on an Oxidative-Stress Model Induced by Microinjection of Sodium Nitroprusside in Mice

“…We have previously established an in vivo brain oxidative stress model induced by intrastriatal microinjection of SNP (27), in order to evaluate the protective effects of antioxidant substances. In this study, using the oxidative stress model, we investigated the protective effect of luteolin against oxidative damage induced by SNPtoxicity.…”

“…We previously reported that iron-related radical reactions had crucial roles in SNP-induced brain damage (27). Thus, in order to elucidate the protective mechanism of luteolin, we used the DPPH method to determine Mice were orally administered luteolin (600 -1200 mg/kg) and after 24 h, SNP (10 nmol) was injected into the right striatum.…”

Neuroprotective Effects of Curcumin and Highly Bioavailable Curcumin on Oxidative Stress Induced by Sodium Nitroprusside in Rat Striatal Cell Culture

“…DPPH Radical-Scavenging Activity We previously reported that iron-related radical reactions have crucial roles in SNP-induced brain damage. 25) Thus, to elucidate the protective mechanism of curcumin, we determined the free radicalscavenging activity of curcumin using DPPH. As shown in Fig.…”