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 for 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.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/s0014-2999(98)00696-7 | DOI Listing |
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!