Hung H C, Lee E H
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Free Radic Biol Med. 1998 Jan 1;24(1):76-84. doi: 10.1016/s0891-5849(97)00206-2.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to produce a differential toxicity in the nigrostriatal and mesolimbic dopaminergic pathways with the nigrostriatal pathway being more vulnerable. We, therefore, investigated whether oxidative stress and the antioxidant system play a role in this phenomenon. Balb/c mice were treated with either saline or MPTP (30 mg/kg/d) for 7 d, and were sacrificed on the next day. Results revealed that MPTP increased lipid peroxidation in the striatum (ST) and decreased glutathione concentration in the substantia nigra (SN) without markedly affecting these measures in the nucleus accumbens (NAc) and ventral tegmental area (VTA). Further, MPTP produced approximately twofold increases in both manganese superoxide dismutase (MnSOD) and copper-zinc superoxide dismutase (CuZnSOD) activities in the VTA while it only increased MnSOD activity in the SN. Both catalase and glutathione peroxidase (GPx) activities were not markedly altered by MPTP in both systems. However, the basal levels of catalase and GPx activities were higher in the VTA and NAc than in the SN and ST. These results together suggest that a lesser degree of oxidative damage and a more inducible CuZnSOD activity observed in the mesolimbic dopaminergic pathway may partially explain the differential toxicity MPTP produced in these two dopaminergic systems.
已知1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）在黑质纹状体和中脑边缘多巴胺能通路中产生不同的毒性，其中黑质纹状体通路更易受损。因此，我们研究了氧化应激和抗氧化系统是否在此现象中起作用。将Balb/c小鼠用生理盐水或MPTP（30mg/kg/d）处理7天，并于次日处死。结果显示，MPTP增加了纹状体（ST）中的脂质过氧化，并降低了黑质（SN）中的谷胱甘肽浓度，而对伏隔核（NAc）和腹侧被盖区（VTA）中的这些指标没有明显影响。此外，MPTP使VTA中的锰超氧化物歧化酶（MnSOD）和铜锌超氧化物歧化酶（CuZnSOD）活性均增加了约两倍，而在SN中仅增加了MnSOD活性。在这两个系统中，MPTP均未明显改变过氧化氢酶和谷胱甘肽过氧化物酶（GPx）的活性。然而，VTA和NAc中过氧化氢酶和GPx活性的基础水平高于SN和ST。这些结果共同表明，在中脑边缘多巴胺能通路中观察到的较低程度的氧化损伤和更高的可诱导性CuZnSOD活性可能部分解释了MPTP在这两个多巴胺能系统中产生的不同毒性。
