Coexistence of zinc and iron augmented oxidative injuries in the nigrostriatal dopaminergic system of SD rats.
Clinical studies have demonstrated an excess of transition metals, including zinc and iron, in the substantia nigra (SN) of Parkinson's patients. In the present study, the neurotoxic effect of zinc was investigated using iron as a positive control. Addition of zinc or iron to brain homogenates increased lipid peroxidation. Zinc was less potent than iron in inducing lipid peroxidation. Coincubation with desferrioxamine prevented zinc- and iron-induced lipid peroxidation. Furthermore, glutathione (GSH), S-nitroso-N-acetylpenicillamine, or melatonin inhibited zinc-induced lipid peroxidation. The oxidative effect of zinc was further investigated in anesthetized rats. Seven days after intranigral infusion of zinc, lipid peroxidation was elevated in the infused SN, and dopamine content and tyrosine hydroxylase-positive axons were decreased in the ipsilateral striatum. Zinc was less potent than iron in inducing neurodegeneration in vivo. L-Buthionine-[S,R]-sulfoximine pretreatment (i.c.v.), which depletes cellular GSH levels, enhanced zinc-induced oxidative injuries in the nigrostriatal dopaminergic system. Moreover, simultaneous infusion of zinc and iron appeared to augment oxidative injuries in rat brain. Taken together, our results demonstrate that intranigral infusion of zinc caused degeneration of the nigrostriatal dopaminergic system in rat brain. Furthermore, coexistence of zinc and iron augmented oxidative injuries in rat brain. These findings indicate that both zinc and iron contribute to the etiology of Parkinsonism.
Lin
A M
AM
Department of Medical Research and Education, Veterans General Hospital-Taipei and Department of Physiology, National Yang-Ming University, Taipei, Taiwan. myalin@vghtpe.gov.tw
D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000201:enzymology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D005978:Glutathione / Q000494:pharmacology; D007501:Iron / Q000008:administration & dosage / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D018384:Oxidative Stress; D020734:Parkinsonian Disorders / Q000209:etiology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D013050:Spectrometry, Fluorescence; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology*
D026423:S-Nitroso-N-Acetylpenicillamine; D007501:Iron; D014446:Tyrosine 3-Monooxygenase; D005978:Glutathione; D010396:Penicillamine; D003676:Deferoxamine; D015032:Zinc; D008550:Melatonin; D004298:Dopamine