Iron-Mediated Free Radical Injury in Ethanol-Exposed Mouse Neural Crest Cells

摘要

Previous studies using cell and whole embryo cutures have shown that free radicals play an important role in the ethanolinduced death of mouse neural crest cells (NCCs;a significant cell type with respect to the genesis of alcohol-related birth defects).This investigation was spurred by reports of increased iron in ethanol-exposed fetuses and the knowledge that iron chelators, deferoxamine and phenanthroline, relative to ethanol-induced ceell death was examined.Cotreatment of cultured NCCs 100 mM ethanol and either 1 or 10 #mu#M deferoxamie or 10,50,or 250 #mu#M phenanthroline significantly increased the percentage of viable cells as compared with exposure to 100 mM ethanol alone. These data indicate that iron is involved in the ethanol-induced cytotoxicity. To support this premise,the direct toxicity of iron to NCCs was also examined. As expected, loading the cells with Fe(II)/Fe(III) using 8-hydroxyquinoline as a carrier had an adverse effect on their viability as did treatment with a neurotoxin, 6-hydroxydopamine, that releases iron from ferritin storage. Cotreatment with an antioxidant, N-acetylcysteine, significantly diminished the toxicity of ethanol alone, that resulting from iron loading, as well as fromthe combination of ethanol exposure and iron loading. These results confirm the role of free readical-mediated damage in ethanol-induced cytotoxicity and highlight the potential role of iron relative to the genesis of alcohol-related birth defects.