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

DOI Web Site PubMed 6 Citations 60 References
  • Nazari Qand Agha
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Mizuno Keita
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Kume Toshiaki
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Takada-Takatori Yuki
    Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College, Japan Department of Pharmacology, Faculty of Pharmaceutical Sciences, Doshisha Women’s College, Japan
  • Izumi Yasuhiko
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Akaike Akinori
    Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Graduate School of Pharmaceutical Sciences, Nagoya University, Japan Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan Graduate School of Pharmaceutical Sciences, Nagoya University, Japan

Search this article

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, FeCl2 (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 FeCl2 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.

Journal

Citations (6)*help

See more

References(60)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top