Paraquat (Figure 12.18) is used widely as a weed killer, hence is often found in the home. Unfortunately paraquat has caused many hundreds of deaths both by accidental and deliberate poisoning, the latter including both suicide and homicide.
Paraquat is a local skin irritant, causing inflammation, although poisoning usually follows oral ingestion. The toxic effects are dose related and with small amounts there may be minimal damage that is reversible. Fatal doses cause a painful death within several days or weeks, with extreme abdominal pain, vomiting and diarrhea. The major target organs are the lungs with larger doses causing alveolar edema, resulting in destruction of lung tissues and fibrosis, if the patient survives beyond a few days. Pulmonary fibrosis and respiratory failure can, however, develop up to six weeks after ingestion. The kidneys, heart and liver may also be damaged but the lungs are particularly susceptible in paraquat poisoning because alveolar epithelial cells actively accumulate paraquat to toxic concentrations. Furthermore, the presence of large concentrations of oxygen in the organs exacerbates the morbid effects. Paraquat in alveolar epithelial cells is reduced by electron donors, such as NADH, to a stable reduced form (Figure 12.19). Given the prevailing aerobic conditions, this transfers an electron to dioxygen to form a superoxide radical:
However, the actions of SOD and catalase are likely to be overwhelmed in aerobic conditions and the superoxide radicals accumulate and react with hydrogen peroxide to give highly toxic hydroxyl radicals, particularly in the presence of ions of transition metals, such as iron and copper:
These lead to a variety of toxic effects, such as lipid peroxidation (Figure 12.20). The resulting lipid peroxides may give rise to lipid radicals and membrane damage leading to tissue damage and fibrosis. Lipid peroxides will also oxidize glutathione (Figure 12.6) and its reoxidation further reduces the depleted amount of NADPH. This reduces the ability of the alveolar cells to carry out essential functions, such as biosynthetic repairs.
There is no antidote for paraquat poisoning and once it has accumulated in the lungs little can be done to prevent its toxic effects. Treatment largely consists of trying to prevent absorption by the gut by gastric lavage and by using Fullers Earth as an adsorbent. Hemoperfusion may also be used to reduce the concentration of any paraquat already absorbed.