Superoxide is not the proximate cause of paraquat toxicity

Paraquat toxicity is thought to occur through the production of superoxide O2(.-) and it has been argued that this oxygen radical species is, itself, an important mediator of the toxicity of this drug. If so, a direct relationship should exist between the steady-state amounts of O2(.-) produced and the lethal effects of paraquat. We have therefore examined O2(.-) mediated chemiluminescence and paraquat sensitivity in bacteria with widely varying superoxide dismutase (SOD) activities. As expected, bacteria with high SOD activity exhibit minimal (lucigenin enhanced) chemiluminescence in the presence of paraquat whereas SOD-deficient bacteria show >90-fold higher chemiluminescence compared to parental strains. Nonetheless, high SOD bacteria are more readily killed by paraquat whereas SOD-deficient organisms show no increased susceptibility to this agent. This further supports our earlier conclusions that hypertrophied SOD activity is inadequate defense against paraquat and that O2(.-) is probably not the proximate toxin by which paraquat mediates cellular injury.