title: Zinc protects Escherichia coli against copper-mediated paraquat-induced damage.
abstract: The essential mediatory role of copper and iron in paraquat-induced biological damage has been recently demonstrated. It was postulated that these transition metals undergo cyclic redox reactions and serve as centers for repeated production of hydroxyl radical, which are the ultimate deleterious agents. Additionally, we had presented evidence indicating efficient protection against paraquat toxicity by agents commonly employed (chelators, chemical scavengers, and protecting enzymes). In this study we have used the Escherichia coli model in order to develop a new approach for protection against paraquat-induced metal-mediated cellular injury. It entails the administration of excess zinc (up to 50-fold over copper), which results in an inhibition of the toxic effect of paraquat. Lineweaver-Burk analysis demonstrates the competitive mode of this inhibition. The suggested mechanism involves either the direct displacement of copper by zinc or the formation of a ternary complex, (formula; see text) in which the binding of Cu(II) is weakened by the binding of Zn(II), interfering with the copper-mediated free radicals formation. Thus, use of redox-inactive metals, which possess high similarity of their ligand chemistry to that of iron and copper but are of relative low toxicity by themselves, should be considered for intervention in paraquat toxicity and in other metal-mediated free radical-induced injurious processes.
authors.affiliation: Department of Cellular Biochemistry, Hebrew University of Jerusalem, Israel.
authors.forename: P
authors.initials: P
authors.lastname: Korbashi
authors.forename: J
authors.initials: J
authors.lastname: Katzhendler
authors.forename: P
authors.initials: P
authors.lastname: Saltman
authors.forename: M
authors.initials: M
authors.lastname: Chevion
mesh_terms: D003300:Copper / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development*; D007700:Kinetics; D010269:Paraquat / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*
chemical_list: D003300:Copper; D015032:Zinc; D010269:Paraquat