Mechanism of Toxicity 

Paraquat concentrates in (pulmonary) alveolar type I and II cells via an energy dependant transport system (due to structural similarity of paraquat with naturally occurring polyamines taken up by alveolar cells).

High concentration of paraquat once accumulated into lung or renal cells results in redox cycling and generation of toxic reactive oxygen species (see diagram). This can overwhelm cellular defence mechanisms and lead to lung damage (acute and subchronic) and renal tubular necrosis.

Renal failure may occur as a result of direct tubular toxicity and haemodynamic changes. It is an early, but often reversible, feature of paraquat poisoning. Maintenance of renal function is important to reduce plasma paraquat levels and thereby minimise accumulation in lung cells.

After large doses multi-organ failure can lead to rapid death. At more intermediate doses, the initial lung injury may appear to repair, but then develop into fibrosis. This is characterised by rapid, excessive proliferation and differentiation of fibroblasts, resulting in a loss of pulmonary architecture and interference with gas exchange. Depletion of surfactant and the inflammatory response may also contribute to further toxicity.