Oxidation of N-methyl(R)salsolinol: involvement to neurotoxicity and neuroprotection by endogenous catechol isoquinolines.

摘要: 1(R), 2(N)-Dimethyl-6,7-dihydroxy-l,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 be ascribed its oxidation into cytotoxic 1,2-dimethyl-6,7dihydroxyisoquinolinium ion with generation hydroxyl radical. isoquinolinium caused massive necrosis the striatum, whereas Nmethyl(R)salsolinol depleted selectively neurons substantia nigra without necrotic tissue reaction. N-Methyl(R)salsolinol induced DNA damage human neuroblastoma SH-SY5Y cells, which could prevented by anti-oxidants and cycloheximide. These results suggest that oxidative stress through induces apoptotic cell death. On other hand, (R)salsolinol scavenge radical produced dopamine. neurotoxicity neuroprotection catechol isoquinolines may their scavenging radicals.