title: Zinc-induced apoptosis in substantia nigra of rat brain: neuroprotection by vitamin D3.
abstract: Accumulation of transition metals has been suggested to be responsible for the deteriorated nigrostriatal dopaminergic system in Parkinson's patients. In the present study, the mechanism underlying the zinc-induced neurotoxicity was investigated in the nigrostriatal dopaminergic system in vivo. Our 6-methoxy-8-paratoluene sulfonamide quinoline fluorescence study showed zinc translocation in the infused nigral cells after intranigral infusion of zinc. Furthermore, lipid peroxidation in the zinc-infused substantia nigra was consistently elevated 4 h to 7 d after the infusion. At the same time, an abrupt increase in cytosolic cytochrome c content in the infused substantia nigra was observed 4 h after zinc infusion and gradually decreased to basal levels 7 d after infusion. Both TUNEL-positive neurons and DNA fragmentation, indicatives of apoptosis, were detected in the zinc-infused substantia nigra. Furthermore, striatal dopamine content was reduced 7 d after the infusion. In attempt to prevent zinc-induced neurotoxicity, vitamin D3 was systemically administered. Zinc-induced increases in lipid peroxidation and cytosolic cytochrome c in the infused substantia nigra were prevented by this treatment. Moreover, zinc-induced reduction in striatal dopamine content was attenuated after vitamin D3 treatment. Our in vivo data suggest that zinc-induced oxidative stress may result in apoptosis followed by reduced dopaminergic function in the nigrostriatal dopaminergic system. Furthermore, vitamin D3 prevented zinc-induced oxidative injuries in the rat brain.
authors.affiliation: Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei, Taiwan
authors.forename: Anya M Y
authors.initials: AM
authors.lastname: Lin
authors.forename: S F
authors.initials: SF
authors.lastname: Fan
authors.forename: D M
authors.initials: DM
authors.lastname: Yang
authors.forename: L L
authors.initials: LL
authors.lastname: Hsu
authors.forename: C H J
authors.initials: CH
authors.lastname: Yang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002762:Cholecalciferol / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D045304:Cytochromes c / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation; D008297:Male; D009474:Neurons / Q000166:cytology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D002762:Cholecalciferol; D045304:Cytochromes c; D015032:Zinc; D004298:Dopamine