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'-tetrakis(2-pyr idylmethyl)-ethylene-diamine (TPEN), co-injected with zinc chloride in vivo, totally prevented zinc-induced neuronal loss. Furthermore, intr ahippocampal 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 messy fibres. This demonstrates that TPEN is taken up by zinc-containing neurones in vivo. The use of TPEN to block the a ctions of zinc could help define the possible role of zinc in the path ology of various neurological disorders.