Marzatico F, Café C, Taborelli M, Benzi G
Institute of Pharmacology, University of Pavia, Italy.
Neurochem Res. 1993 Oct;18(10):1101-6. doi: 10.1007/BF00966691.
The effects of the Parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were evaluated in four different monkey brain areas (frontal and occipital cortex, caudate putamen, substantia nigra). The basal and stimulated lipid peroxidation and the reduced glutathione (GSH) concentration were evaluated in three groups of male Macaca fascicularis monkeys (6 animals/group): (a) controls; (b) MPTP-treated animals; (c) animals treated with MPTP and alpha-dihydroergocryptine (DEK; ergot alkaloid characterized by a dopaminergic agonist action). In MPTP-treated animals the GSH concentration was unchanged or decreased in a non-significant way in the frontal and occipital cortex, and in substantia nigra. The basal thiobabituric acid reactive substance (TBARS) concentrations were significantly higher in the caudate putamen and substantia nigra of MPTP-treated animals. In the MPTP-treated monkeys the DEK administration induced a restoration of basal TBARS values to nearly normal ones. By incubating tissue from different brain areas with FeSO4 plus ascorbic acid, the stimulation of lipid peroxidation decreased the TBARS production in the substantia nigra of the MPTP-treated animals. These results, taken together, may indicate that an increased lipid peroxidation could possibly play a role in producing the Parkinson-like syndrome by MPTP and that a free radical excess could be responsible for the degeneration of the substantia nigra. The treatment with an ergot alkaloid (i.e., alpha-dihydroergocryptine) partially antagonizes the MPTP-induced increase in basal TBARS concentration in caudate putamen.
在四个不同的猴脑区域（额叶和枕叶皮质、尾状壳核、黑质）评估了神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱发的帕金森症的影响。在三组雄性食蟹猴（每组6只动物）中评估了基础和刺激状态下的脂质过氧化以及还原型谷胱甘肽（GSH）浓度：（a）对照组；（b）MPTP处理组动物；（c）MPTP和α-二氢麦角隐亭（DEK；一种具有多巴胺能激动剂作用的麦角生物碱）处理组动物。在MPTP处理组动物中，额叶和枕叶皮质以及黑质中的GSH浓度未发生变化或仅有非显著性降低。MPTP处理组动物的尾状壳核和黑质中基础硫代巴比妥酸反应性物质（TBARS）浓度显著更高。在MPTP处理的猴子中，给予DEK可使基础TBARS值恢复至接近正常水平。通过用硫酸亚铁加抗坏血酸孵育不同脑区的组织，脂质过氧化刺激降低了MPTP处理组动物黑质中的TBARS生成。综合这些结果可能表明，脂质过氧化增加可能在MPTP诱发帕金森样综合征中起作用，自由基过量可能是黑质变性的原因。用麦角生物碱（即α-二氢麦角隐亭）治疗可部分拮抗MPTP诱导的尾状壳核中基础TBARS浓度升高。
