Copper-mediated toxicity of 2,4,5-trichlorophenol: biphasic effect of the copper(I)-specific chelator neocuproine.
The lipophilic copper(I)-specific chelator neocuproine has been frequently used as an inhibitor of copper-mediated damage in biological systems. In this communication we report that the copper-mediated toxicity of 2,4,5-trichlorophenol is markedly potentiated by neocuproine at levels which are near-stoichiometric with respect to the copper concentration but is inhibited at higher concentrations. However, no potentiation was observed when neocuproine was substituted by bathocuproinedisulfonic acid, a negative charged ligand with essentially the same copper-binding characteristics as neocuproine. We found that the potentiation by neocuproine was due to the formation of a lipophilic copper complex, while the inhibition by bathocuproinedisulfonic acid was due to the formation of a hydrophilic one. Caution in the use of neocuproine to study copper-mediated toxicity is advised.
Department of Cellular Biochemistry, Hebrew University-Hadassah Schools of Medicine and Dental Medicine, Jerusalem, 91120, Israel. benzhan.zhu@orst.edu
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D002374:Catalase / Q000494:pharmacology; D002614:Chelating Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002733:Chlorophenols / Q000008:administration & dosage / Q000633:toxicity*; D003300:Copper / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D010084:Oxidation-Reduction; D010618:Phenanthrolines / Q000008:administration & dosage / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology
D002614:Chelating Agents; D002733:Chlorophenols; D016166:Free Radical Scavengers; D010618:Phenanthrolines; C009534:2,4,5-trichlorophenol; D000431:Ethanol; C028559:bathocuproine sulfonate; D003300:Copper; C002701:neocuproine; D002374:Catalase; D013482:Superoxide Dismutase; D004121:Dimethyl Sulfoxide