Effects of cytisine on hydroxyl radicals in vitro and MPTP-induced dopamine depletion in vivo

The potential new iron-chelator cytisine and the radical scavenger N-tert-butyl-alpha-(2-sulfophenyl) nitrone (S-PBN) were incubated in a Fenton system and hydroxyl radical formation was measured with the salicylate trapping assay. Both cytisine and S-PBN reduced hydroxyl radical formation in a concentration-dependent manner. For in vivo studies, C57BL/6 mice were injected repeatedly with cytisine (0.5 mg/kg or 2.0 mg/kg s.c.) or saline seven days before and after a single 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) injection (30 mg/kg s.c.). Seven days after MPTP treatment alone dopamine levels were significantly reduced to 12% of the control values (p < 0.001), whereas MPTP + cytisine treatment (2 mg/kg) led to more than twofold higher dopamine levels (p < 0.01) compared with MPTP alone. We have shown fbr the first time that cytisine attenuates hydroxyl radical formation in vitro and reduces MPTP-induced dopamine depletion. Thus, cytisine may be useful for the treatment of Parkinson's Disease where the chelation of iron ions could prevent neuronal cell death. (C) 1998 Elsevier Science B.V. All rights reserved.