Wan F J, Lin H C, Huang K L, Tseng C J, Wong C S
Institute of Undersea and Hyperbaric Medicine, National Defense Medical Center, P.O. Box 90048-516, Taipei 100, Taiwan, R.O.C.
Life Sci. 2000 Mar 3;66(15):PL205-12. doi: 10.1016/s0024-3205(00)00458-6.
The long-term effect of d-amphetamine (AMPH) on the induction of oxidative stress was examined in vivo in the rat brain. In this study, 2,3-dihydroxybenzoic acid (2,3-DHBA) and malonaldehyde (MDA) were used as the index of the hydroxyl radical and lipid peroxidation, respectively. The levels of 2,3-DHBA, MDA and dopamine (DA) in striatal homogenates were examined 7 days following injection of a single large dose of AMPH (7.5 mg/kg, i.p.) in rats pretreated with desipramine (10 mg/kg, i.p.), an agent that inhibits the metabolism of AMPH. Our results showed that 2,3-DHBA and MDA levels were significantly increased by AMPH, whereas DA and its metabolites, DOPAC and HVA were depleted in the striatum. Pretreatment with the glutamate NMDA receptor subtype antagonist MK-801 (1 mg/kg, i.p.) attenuated the increases of 2,3-DHBA and MDA, and provided partial protection against the long-lasting loss of DA produced by AMPH. Overall, the results demonstrate that AMPH could induce sustained production of free radical and oxidative damage, and lead to DA terminal degeneration in the striatum of the rat.
在大鼠脑中对右旋苯丙胺（AMPH）诱导氧化应激的长期影响进行了体内研究。在本研究中，分别使用2,3 - 二羟基苯甲酸（2,3 - DHBA）和丙二醛（MDA）作为羟基自由基和脂质过氧化的指标。在给予抑制AMPH代谢的药物地昔帕明（10 mg/kg，腹腔注射）预处理的大鼠中，单次大剂量注射AMPH（7.5 mg/kg，腹腔注射）7天后，检测纹状体匀浆中2,3 - DHBA、MDA和多巴胺（DA）的水平。我们的结果表明，AMPH显著提高了2,3 - DHBA和MDA的水平，而纹状体中的DA及其代谢产物3,4 - 二羟基苯乙酸（DOPAC）和高香草酸（HVA）则减少。用谷氨酸NMDA受体亚型拮抗剂MK - 801（1 mg/kg，腹腔注射）预处理可减弱2,3 - DHBA和MDA的升高，并对AMPH引起的DA长期损失提供部分保护。总体而言，结果表明AMPH可诱导自由基的持续产生和氧化损伤，并导致大鼠纹状体中DA终末变性。
