Antioxidative effect of vitamin D3 on zinc-induced oxidative stress in CNS.
Antioxidative mechanisms of vitamin D3 were evaluated both in vitro and in vivo. A 4-h incubation of brain homogenates at 37 degrees C increased the formation of Schiff base fluorescent products of malonaldehyde, an indicator of lipid peroxidation. Incubation with vitamin D3 dose-dependently suppressed auto-oxidation. The antioxidative potency for inhibiting zinc-induced lipid peroxidation was as follows: vitamin D3 > Trolox (a water-soluble analogue of vitamin E) > or = beta-estradiol > melatonin. In the presence of high dose of desferrioxamine, a metal chelator, vitamin D3 attenuated auto-oxidation. These in vitro data indicate that vitamin D3 may act as a terminator of the lipid peroxidation chain reaction. The antioxidative effect of vitamin D3 on zinc-induced oxidative injury was verified using local infusion of vitamin D3 in vivo. Intranigral infusion of zinc elevated lipid peroxidation in the infused substantia nigra and depleted striatal dopamine content at 7 days after infusion. Furthermore, elevated cytosolic cytochrome c and DNA ladder, indicatives of apoptosis, were demonstrated in the infused substantia nigra. Simultaneous infusion of vitamin D3 and zinc prevented oxidative injury and apoptosis induced by zinc alone. The involvement of glia-derived neurotrophic factor (GDNF) expression was excluded since vitamin D3 did not alter GDNF level in the infused substantia nigra at 24 h or 4 days after intranigral infusion of vitamin D3. Our results suggest that vitamin D3, independent of upregulation of GDNF expression, may acutely prevent zinc-induced oxidative injuries via antioxidative mechanisms.
Lin
Anya M Y
AM
Department of Medical Research and Education, Veterans General Hospital-Taipei, Taipei 112, Taiwan. myalin@vghtpe.gov.tw
Chen
K B
KB
Chao
P L
PL
D000818:Animals; D000975:Antioxidants; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002490:Central Nervous System / Q000378:metabolism*; D002762:Cholecalciferol / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry; D016166:Free Radical Scavengers / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism; D007150:Immunohistochemistry; D007267:Injections; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra; D015032:Zinc / Q000633:toxicity*
D000975:Antioxidants; D016166:Free Radical Scavengers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D002762:Cholecalciferol; D045304:Cytochromes c; D003676:Deferoxamine; D015032:Zinc; D004298:Dopamine