Figure 1. Redox cycling by paraquat.

Paraquat is a highly toxic quarternary nitrogen herbicide which has been shown capable to redox cycle in some cell types. Dication paraquat (PQ²⁺) is reduced to PQ⁺ by an NADPH-cytochrome P450 reductase. In the presence of O₂, PQ²⁺ is oxidized with the concomitant production of superoxide anion (•O₂⁻). SOD dismutates •O₂⁻ to H₂O₂ which is further metabolized by GPX. •O₂⁻ also reacts •NO leading to the formation of ONOO⁻. Overexpression of SOD and GPX protects against paraquat-induced toxicity [107]. However, PQ²⁺ can redox cycle again, leading to a continuous generation of ROS and oxidative stress, and depleting the intracellular pools of GSH and NADPH (required for GSSG recycling to GSH by GR). Accumulation of H₂O₂ is reduced further to •OH⁻ through Fenton type reactions.