Melatonin suppresses iron-induced neurodegeneration in rat brain.
The antioxidative action of melatonin on iron-induced neurodegeneration in the nigrostriatal dopaminergic system was evaluated in vivo. Intranigral infusion of iron chronically degenerated the dopaminergic transmission of the nigrostriatal system. An increase in lipid peroxidation in the infused substantia nigra and reductions in dopamine levels and dopaminergic terminals in the ipsilateral striatum were observed 7 d after iron infusion. Whereas local infusion of melatonin (60 microg/microl, 1 microl) alone did not alter dopaminergic transmission, coinfusion of melatonin with iron suppressed iron-induced oxidative damages. Systemic infusion of melatonin via osmotic pumps had no effect on iron-induced neurodegeneration. However, repetitive intraperitoneal injections of melatonin (10 mg/kg) prevented iron-induced oxidative injuries. The ratio of glutathione (GSH)/oxidized glutathione (GSSG) was moderately increased in the lesioned substantia nigra of the melatonin-treated rats compared to that of the lesioned group in control rats. The antioxidative effect of melatonin was verified in cortical homogenates. Melatonin dose-dependently suppressed autoxidation and iron-induced lipid peroxidation. Melatonin was as effective as GSH and was less effective than Trolox (a water-soluble analogue of vitamin E) in inhibiting iron-elevated lipid peroxidation of brain homogenates. Our data suggest that melatonin is capable of at least partially preventing the iron-induced neurodegeneration in the nigrostriatal dopaminergic system.
Lin
A M
AM
Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei, Taiwan.
Ho
L T
LT
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002839:Chromans / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology; D007150:Immunohistochemistry; D015918:Infusion Pumps, Implantable; D007501:Iron; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000139:chemically induced* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D002839:Chromans; D007501:Iron; D005978:Glutathione; D008550:Melatonin; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004298:Dopamine