Effects of α-phenyl-N-tert-butyl nitrone and N-acetylcysteine on hydroxyl radical formation and dopamine depletion in the rat striatum produced by D-amphetamine
Effects of α-phenyl-N-tert-butyl nitrone and N-acetylcysteine on hydroxyl radical formation and dopamine depletion in the rat striatum produced by D-amphetamine
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DOI：
10.1016/j.euroneuro.2005.07.002
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发表时间：
2006-02-01
影响因子：
5.6
通讯作者：
Lin, HC
中科院分区：
文献类型：
--
作者：
Wan, FJ;Tung, CS;Lin, HC
先前的研究表明，自由基清除剂治疗可减轻 D-安非他明 (AMPH) 的神经毒性。但其中一些药物也能防止 AMPH 引起的大鼠体温升高。因此，需要进一步的研究来确定自由基产生的阻断或低温是否与自由基清除剂对 AMPH 神经毒性的神经保护机制有关。在本研究中，我们研究了自由基清除剂 α-苯基-N-叔丁基硝酮 (PBN) 和 N-乙酰半胱氨酸 (NAC) 对纹状体多巴胺 (DA) 长期消耗和脂质过氧化形成以及 AMPH 诱导的高热的影响。我们还确定了直接纹状体内输注 AMPH 后它们对急性羟自由基形成的影响。结果表明，在不阻断 AMPH 诱导的高热的剂量范围内，两者均显着减弱大鼠纹状体中的长期 DA 消耗和脂质过氧化形成。这些药物还完全抑制了 AMPH 输注至纹状体后羟自由基的产生。我们的研究结果表明，PBN 和 NAC 等自由基清除剂可以通过其自由基清除特性来防止 AMPH 诱导的氧化应激和 DAergic 末端毒性，而不依赖于降低大鼠的核心体温，这意味着补充抗氧化剂是治疗 AMPH 神经毒性的潜在策略。 (c) 2005 Elsevier B.V. 和 ECNP。版权所有。
Previous studies have shown that treatment with free radical scavengers attenuated the D-amphetamine (AMPH) neurotoxicity. But several of these agents also prevent AMPH-induced elevation of body temperature in the rat. Thus, further studies are needed to determine if blockade of the production of free radical or hypothermia are related to the neuroprotective mechanism of the free radical scavengers for AMPH neurotoxicity. In the present study, we examined the effects of the free radical scavengers alpha-phenyt-N-tert-butyl nitrone (PBN) and N-acetylcysteine (NAC) on long-term depletion of striatal dopamine (DA) and lipid peroxidation formation and on hyperthermia induced by AMPH. We also determined their effects on acute hydroxyl radical formation after direct intrastriatal infusion of AMPH. The results showed that both significantly attenuated long-term DA depletion and lipid peroxidation formation in the rat striatum at the dose range that did not block hyperthermia induced by AMPH. These agents also completely inhibited the production of hydroxyl radical after AMPH infusion into the striatum. Our results suggest that free radical scavengers such as PBN and NAC could protect against AMPH-induced oxidative stress and DAergic terminal toxicity via their free radical removing property independent of lowering the core body temperature of rats, and imply that supplement with antioxidants is a potential strategy in the treatment of AMPH neurotoxicity. (c) 2005 Elsevier B.V. and ECNP. All rights reserved.