Ogawa N, Asanuma M, Kondo Y, Kawada Y, Yamamoto M, Mori A
Department of Neuroscience, Institute of Molecular and Cellular Medicine, Okayama University Medical School, Japan.
Neurosci Lett. 1994 Apr 25;171(1-2):55-8. doi: 10.1016/0304-3940(94)90603-3.
Whether or not chronic L-dopa treatment (100 mg/kg, intraperitoneally (i.p.), twice daily for 4 weeks) alters lipid peroxidation in the brain as an indicator of neuronal damage was examined in normal mice and mice in which catecholamine (CA) neurons had been injured previously by the administration of 6-hydroxydopamine (6-OHDA), followed by recovery. In normal mice, chronic L-dopa treatment reduced the thiobarbituric acid reacting substances (TBARS) level, an indicator of lipid peroxidation, in the cerebral cortex. In contrast, in mice with CA neuronal injury induced by pretreatment with 6-OHDA, the chronic L-dopa treatment markedly increased the TBARS in the striatum and frontal cortex, despite recovery of the striatal dopamine levels similar to those in the control mice. These findings suggest that the long-term high-dose administration of L-dopa enhances the progression of neuronal damage in patients with injured CA neurons such as those with Parkinson's disease.
研究了慢性左旋多巴治疗（100毫克/千克，腹腔注射（i.p.），每日两次，共4周）是否会改变大脑中的脂质过氧化作用，以此作为神经元损伤的指标，实验对象为正常小鼠以及先前通过注射6-羟基多巴胺（6-OHDA）损伤儿茶酚胺（CA）神经元后恢复的小鼠。在正常小鼠中，慢性左旋多巴治疗降低了大脑皮层中硫代巴比妥酸反应物质（TBARS）水平，这是脂质过氧化作用的一个指标。相比之下，在经6-OHDA预处理诱导CA神经元损伤的小鼠中，尽管纹状体多巴胺水平恢复到与对照小鼠相似，但慢性左旋多巴治疗显著增加了纹状体和额叶皮层中的TBARS。这些发现表明，长期高剂量施用左旋多巴会加速患有CA神经元损伤的患者（如帕金森病患者）的神经元损伤进程。
