Desferrioxamine and vitamin E protect against iron and MPTP-induced neurodegeneration in mice.
To elucidate the neuroprotective effects of the iron chelator desferrioxamine (DFO) and the antioxidant vitamin E on excessive iron-induced free radical damage, a chronic iron-loaded mice model was established. The relationship between striatal iron content, oxidized to reduced glutathione ratio, hydroxyl radical (.OH) levels and dopamine concentrations were observed in DFO or vitamin E pretreated iron-loaded/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated C57BL/6 mice. The results demonstrated that both DFO and vitamin E inhibit the iron accumulation and thus reverses the increase in oxidized glutathione (GSSG), oxidized to reduced glutathione ratios, .OH and lipid peroxidation levels. The striatal dopamine concentration was elevated to normal value. Our data suggested that: (1) iron may induce neuronal damage and thus excessive iron in the brain may contribute to the neuronal loss in PD; (2) iron chelators and antioxidants may serve as potential therapeutic agents in retarding the progression of neurodegeneration.
Lan
J
J
Tianjin Medical University Hospital, Tianjin Neurological Institute, P.R. China.
Jiang
D H
DH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D003342:Corpus Striatum / Q000378:metabolism; D003676:Deferoxamine / Q000627:therapeutic use*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D051379:Mice; D009410:Nerve Degeneration; D009994:Osmolar Concentration; D014810:Vitamin E / Q000627:therapeutic use*
D008054:Lipid Peroxides; D015102:3,4-Dihydroxyphenylacetic Acid; D014810:Vitamin E; D017665:Hydroxyl Radical; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D007501:Iron; D005978:Glutathione; D003676:Deferoxamine; D019803:Glutathione Disulfide; D004298:Dopamine