Quinacrine attenuates increases in divalent metal transporter-1 and iron levels in the rat hippocampus,after kainate-induced neuronal injury

The present investigation was carried out to elucidate the effect of the antimalarial drug quinacrine on levels of expression of the non-heme iron transporter, divalent metal transporter-1 (DMT1) and iron, in the hippocampus of rats after kainate treatment. The untreated hippocampus was lightly stained for DMT1, while an increase in DMT1 staining in astrocytes in the degenerating cornu ammonis (CA) fields, after kainate lesions. The increased DMT1 immunoreactivity was correlated with increased levels of Fe3+ and Fe2+ staining in the CA fields, as demonstrated by iron histochemistry (Perl's and Turnbull's blue stain for Fe3+ and Fe2+). The increases in DMT1 and iron staining were significantly attenuated by quinacrine. Rats injected with kainate and daily i.p. injections of quinacrine (5 mg/kg) for 7 days or 2 weeks showed significantly lower levels of DMT1 immunoreactivity and iron staining, compared with rats injected with kainate and saline. These results show that DMT1 expression is closely linked to iron levels, and provide further support for a crucial role that DMT1 plays in iron accumulation in the degenerating hippocampus.