Lipid peroxidation in brain: interactions of L-DOPA/dopamine with ascorbate and iron.
Recent reports have stressed an accumulation of iron and enhanced levels of lipid peroxides in the substantia nigra as essential factors in the pathogenesis of Parkinson's disease. Many investigators believe that tissue antioxidants, such as ascorbate, play a protective role. On the other hand, L-DOPA, which is used extensively to treat Parkinson's disease, undergoes autoxidation (as does dopamine), thus generating reactive oxygen species. We studied lipid peroxidation (LPO) in mouse brain homogenates and evaluated the effects of iron (5 microM ferric-ADP), L-DOPA, dopamine and ascorbic acid, added either alone or in mixtures. Ascorbic acid was used at levels of 0.5 mM or 2.0 mM, approximating those present normally in brain. LPO in brain homogenates was stimulated by the addition of either ascorbic acid or iron, as well as by a combination of the two, in agreement with other reports. The effects of L-DOPA were complex: L-DOPA strongly suppressed LPO both with and without added iron-ADP. In sharp contrast, however, when ascorbic acid was also added, L-DOPA no longer suppressed LPO; indeed, L-DOPA stimulated LPO in the presence of added iron and ascorbic acid. Dopamine behaved similarly to L-DOPA. When ascorbic acid was studied over a concentration range, LPO was stimulated at 0.5, 1, 2 or 3 mM, with or without added iron and/or dopamine; 5 and 10 mM ascorbic acid were either not as effective or suppressed LPO below control levels. Deferoxamine, a powerful iron chelator, greatly suppressed LPO under all conditions, as did diethylenetriaminepentaacetate (DTPA). Added superoxide dismutase had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Li
C L
CL
Department of Neurology, Mount Sinai School of Medicine, City University of New York, NY 10029, USA.
Werner
P
P
Cohen
G
G
D000818:Animals; D001205:Ascorbic Acid / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D007501:Iron / Q000502:physiology*; D007980:Levodopa / Q000502:physiology*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D051379:Mice
D007980:Levodopa; D007501:Iron; D001205:Ascorbic Acid; D004298:Dopamine