Iron mediates paraquat toxicity in Escherichia coli

J Biol Chem. 1986 Sep 25;261(27):12472-6.

Abstract

The role of iron ions in paraquat toxicity was studied in bacterial system. We show that addition of ferrous iron led to an enhancement of the bacterial killing, whereas addition of chelating agents, such as nitrilotriacetate and desferrioxamine, markedly reduced, up to a total abolishment, the toxic effects. The calculated rates of bacterial killing are proportional to both paraquat and iron concentrations, and conform to the rate equation: dN/dt = -k[paraquat] [Fe2+]. The killing constant for iron, k, is 24-fold smaller than the corresponding value for copper. Mannitol, an OH. scavenger, has a partial protective effect: 15-35% at concentrations range of 1-50 mM, respectively. Histidine, on the other hand, provided a more efficient protection that may be due to a combination of various effects. Induction of endogenous superoxide dismutase and catalase provided partial protection (about 25%). These findings, together with an earlier study on the role of copper in paraquat toxicity (Kohen, R., and Chevion, M. (1985) Free Rad. Res. Commun. 1, 79-88) indicate that transition metals play a central catalytic role in the production of the deleterious effects of paraquat, probably by redox cycling and producing OH. via the site-specific Fenton reaction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalase / biosynthesis
  • Deferoxamine / pharmacology
  • Drug Synergism
  • Enzyme Induction
  • Escherichia coli / drug effects*
  • Histidine / pharmacology
  • Hydroxides
  • Hydroxyl Radical
  • Iron / metabolism*
  • Mannitol / pharmacology
  • Mathematics
  • Nitrilotriacetic Acid / pharmacology
  • Paraquat / toxicity*
  • Superoxide Dismutase / biosynthesis

Substances

  • Hydroxides
  • Hydroxyl Radical
  • Mannitol
  • Histidine
  • Iron
  • Catalase
  • Superoxide Dismutase
  • Deferoxamine
  • Nitrilotriacetic Acid
  • Paraquat