Evaluation of the pro-oxidant and antioxidant actions of L-DOPA and dopamine in vitro: implications for Parkinson's disease.
The antioxidant and pro-oxidant properties of L-DOPA and dopamine were investigated in vitro. Both compounds inhibited the peroxidation of ox-brain phospholipids, with IC50 values of 8.5 microM for dopamine and 450 microM for L-DOPA. Dopamine and L-DOPA reacted with trichloromethyl peroxyl radicals (CCl3O2.) with rate constants of 2.1 x 10(7)M-1s-1 and 1.3 x 10(7)M-1s-1 respectively. The effects of dopamine and L-DOPA on iron ion-dependent hydroxyl radical generation from H2O2 were complex. In general, low concentrations stimulated OH. formation in the presence of ferric-EDTA and, in the case of L-DOPA, ferric-ADP and ferric citrate chelates. Both compounds also reacted with superoxide radical and hypochlorous acid. The products of the reaction with HOCl could still inhibit alpha 1-antiproteinase and appear to be 'long lived' chloramine-type oxidizing species. Our results suggest that L-DOPA and dopamine might have a complex mixture of pro- and anti- oxidant effects, which could contribute to tissue damage due to oxidative stress in Parkinson's disease and other neurological disorders.
Spencer
J P
JP
Neurodegenerative Diseases Research Centre, University of London King's College, UK.
Jenner
A
A
Butler
J
J
Aruoma
O I
OI
Dexter
D T
DT
Jenner
P
P
Halliwell
B
B
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D004295:Dihydroxyphenylalanine / Q000378:metabolism / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D016166:Free Radical Scavengers; D017665:Hydroxyl Radical / Q000378:metabolism; D006997:Hypochlorous Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008081:Liposomes / Q000378:metabolism; D008297:Male; D016877:Oxidants / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy*; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism
D000975:Antioxidants; D015259:Dopamine Agents; D016166:Free Radical Scavengers; D008081:Liposomes; D016877:Oxidants; D013481:Superoxides; D017665:Hydroxyl Radical; D004295:Dihydroxyphenylalanine; D006997:Hypochlorous Acid; D010100:Oxygen; D004298:Dopamine