Prevention of zinc neurotoxicity in vivo by N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN)

Intrahippocampal injections of zinc chloride (10 nmol) produce lesions in the rat hippocampus. A heavy metal chelator N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylene-diamine (TPEN), co-injected with zinc chloride in vivo, totally prevented zinc-induced neuronal loss. Furthermore, intrahippocampal injections of TPEN (10 nmol) were non-toxic when compared with controls. TPEN injections in vivo quenched the in vitro staining of brain sections for zinc (Timm's stain), particularly the staining of the hippocampal mossy fibres. This demonstrates that TPEN is taken up by zinc-containing neurones in vivo. The use of TPEN to block the actions of zinc could help define the possible role of zinc in the pathology of various neurological disorders.