The purpose of this study was to establish a chronic model of
paraquat-induced
lung injury. To examine the role of
reactive oxygen species in this form of
lung injury, we measured
malondialdehyde (MDA) and
superoxide dismutase (SOD) activity in the lungs.
Paraquat (5 mg/kg intramuscularly) caused a significant decrease in dynamic lung compliance from 128.5 +/- 9.2 to 63.3 +/- 11.8 ml/cm H2O (p less than 0.05), with a significant increase in AaPO2 3 wk after
paraquat. Histologic findings in the lungs showed a gradual increase in the number of granulocytes and alveolar wall thickening with proliferation of
reticular fibers and were coincident with the changes in physiology. A transient decrease in pressor responses to
hypoxia was observed 1 wk after
paraquat, although pulmonary hemodynamics did not change. The amount of lung MDA 3 wk after
paraquat increased from the baseline value of 0.73 +/- 0.04 to 1.12 +/- 0.10 nmol/mg
protein (p less than 0.05). SOD activity in the lung tissue significantly decreased from 6.47 +/- 0.20 to 4.82 +/- 0.25 U/mg
protein (p less than 0.05) 1 wk after
paraquat and remained at low levels for 3 wk. These findings suggest that a small dose of
paraquat causes
chronic lung injury characterized by granulocyte infiltration and lung
fibrosis.
Reactive oxygen species may play an important role in this
chronic lung injury, and the inability to increase
antioxidant defense may contribute to the reaction.