A possible mechanism of iron neurotoxicity.
Iron-dependent microsomal lipid peroxidation and catechol-iron (copper)-induced lipid peroxidation have been studied to prove possible nigrostriatal cell damage. Iron-dependent microsomal lipid peroxidation could be initiated by reduced irons coordinated with phosphate moieties in the membranes and significantly inhibited by copper salicylate (hydrophobic and permeable O2-scavenger) and desferrioxamine (a powerful iron-chelating agent), but not by SOD. Ferric or cupric ion significantly promoted a peroxidative cleavage in liposomes (model membranes) after coordinating with dopa or dopamine. Either alpha-tocopherol or desferrioxamine completely abolished the dopa-Fe3+ complex-induced phospholipid peroxidation, while SOD, catalase or sodium benzoate did not. A ferroxidase, ceruloplasmin, significantly inhibited the lipid peroxidation induced by the dopa-Fe3+ complex, indicating the importance of the reduction of iron moiety in the complex for the lipid peroxidation. On the basis of the results obtained with these model systems, nigrostriatal damage by iron had been discussed.
Photon Medical Research Center, Hamamatsu University School of Medicine, Shizuoka, Japan.
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Nakano
D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007501:Iron / Q000493:pharmacokinetics / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects* / Q000502:physiology; D008862:Microsomes, Liver / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats
D007093:Imidazoles; D009498:Neurotoxins; D011719:Pyrazines; C063412:2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo(1,2-alpha)pyrazin-3-one; D007501:Iron