title: In vivo brain oxidative stress model induced by microinjection of sodium nitroprusside in mice.
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.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Qand Agha
authors.initials: QA
authors.lastname: Nazari
authors.forename: Keita
authors.initials: K
authors.lastname: Mizuno
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takada-Takatori
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Izumi
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D005296:Ferrous Compounds / Q000633:toxicity; D005978:Glutathione / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology*; D018384:Oxidative Stress; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D005296:Ferrous Compounds; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D005978:Glutathione; D003676:Deferoxamine; C029451:ferrous chloride