Copper Neurotoxicity in Rat Substantia Nigra and Striatum Is Dependent on DT-Diaphorase Inhibition

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• 作者：Gabriela Dí ; az-Vé ; liz ; Irmgard Paris ; Sergio Mora ; Rita Raisman-Vozari ; and Juan Segura-Aguilar
• 刊名：Chemical Research in Toxicology
• 出版年：2008
• 出版时间：June 2008
• 年：2008
• 卷：21
• 期：6
• 页码：1180-1185
• 全文大小：7,705k
• 年卷期：v.21,no.6(June 2008)
• ISSN：1520-5010

文摘

The dependence of copper neurotoxicity on DT-diaphorase inhibition was suggested from results obtained from a cell line derived from substantia nigra. Therefore, the aim of this study was to evaluate whether CuSO₄ neurotoxicity in vivo, which was evaluated by determining the contralateral rotation and loss of tyrosine hydroxylase immunostaining, was dependent on DT-diaphorase inhibition by dicoumarol. Animals unilaterally and intranigrally injected with 0.25 nmol of CuSO₄ and 2 nmol of dicoumarol presented a significant and characteristic contralateral rotational behavior (P < 0.01) when they were systemically stimulated with apomorphine (0.5 mg/kg s.c.), similar to that observed in rats injected unilaterally with 6-hydroxydopamine as a positive control. The behavioral effects correlated with the lost of tyrosine hydroxylase-positive staining, since animals unilaterally and intranigrally injected with 0.25 nmol of CuSO₄ together with 2 nmol of dicoumarol exhibited extensive loss of tyrosine hydroxylase-positive fiber density in the striatum (P < 0.01) and cell loss in the substantia nigra (P < 0.01). Our results support the idea that CuSO₄ neurotoxicity is dependent upon DT-diaphorase inhibition.