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 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.
Ferger
B
B
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Germany. ferger@mailer.uni-marburg.de
Spratt
C
C
Teismann
P
P
Seitz
G
G
Kuschinsky
K
K
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001392:Azocines; D001557:Benzenesulfonates / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011807:Quinolizines; D000093843:Quinolizidine Alkaloids
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000470:Alkaloids; D001392:Azocines; D001557:Benzenesulfonates; D004298:Dopamine; D015259:Dopamine Agents; D017665:Hydroxyl Radical; D018696:Neuroprotective Agents; D011807:Quinolizines; C094272:N-tert-butyl-(2-sulfophenyl)nitrone; C004712:cytisine; D000093843:Quinolizidine Alkaloids