Naoi M, Maruyama W, Kasamatsu T, Dostert P
Department of Biosciences, Nagoya Institute of Technology, Japan.
J Neural Transm Suppl. 1998;52:125-38. doi: 10.1007/978-3-7091-6499-0_14.
1(R), 2(N)-Dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl(R)salsolinol, is a potent dopaminergic neurotoxin to induce parkinsonism in rats. The cytotoxicity of N-methyl(R)salsolinol proved to be ascribed to its oxidation into cytotoxic 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion with generation of hydroxyl radical. The isoquinolinium ion caused massive necrosis in the striatum, whereas N-methyl(R)salsolinol depleted selectively dopaminergic neurons in the substantia nigra without necrotic tissue reaction. N-Methyl(R)salsolinol induced DNA damage to human neuroblastoma SH-SY5Y cells, which could be prevented by anti-oxidants and cycloheximide. These results suggest that oxidative stress through oxidation of N-methyl(R)salsolinol induces apoptotic cell death. On the other hand, (R)salsolinol proved to scavenge hydroxyl radical produced by oxidation of dopamine. The neurotoxicity and neuroprotection of catechol isoquinolines may be ascribed to their oxidation and scavenging of radicals.
1(R),2(N)-二甲基-6,7-二羟基-1,2,3,4-四氢异喹啉，N-甲基(R)萨索林醇，是一种能在大鼠中诱发帕金森症的强效多巴胺能神经毒素。事实证明，N-甲基(R)萨索林醇的细胞毒性归因于其氧化为具有细胞毒性的1,2-二甲基-6,7-二羟基异喹啉鎓离子并产生羟基自由基。异喹啉鎓离子在纹状体中引起大量坏死，而N-甲基(R)萨索林醇则选择性地使黑质中的多巴胺能神经元减少，且无坏死组织反应。N-甲基(R)萨索林醇对人神经母细胞瘤SH-SY5Y细胞造成DNA损伤，抗氧化剂和环己酰亚胺可预防这种损伤。这些结果表明，N-甲基(R)萨索林醇氧化产生的氧化应激诱导细胞凋亡。另一方面，(R)萨索林醇可清除多巴胺氧化产生的羟基自由基。儿茶酚异喹啉的神经毒性和神经保护作用可能归因于它们的氧化和自由基清除作用。
