PARAQUAT-INDUCED INJURY OF TYPE-II ALVEOLAR CELLS - AN INVITRO MODEL OF OXIDANT INJURY

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Abstract
Paraquat, a widely used herbicide, causes severe, often fatal lung damage. In vivo studies suggested the alveolar epithelial cells (types 1 and 2) were specific targets of paraquat toxicity. This study used 51Cr-labeled type 2 cells from rats to demonstrate that paraquat (10-5 M) resulted in type 2 cell injury in vitro, independent of interacting immune effector agents. With 51Cr release expressed as the cytotoxic index (Cl), type 2 cell injury accelerated with increasing paraquat concentrations (10-5, 10-4 and 10-3 M, resulting in a Cl of 12.5 .+-. 2.2, 22.8 .+-. 1.8 and 35.1 .+-. 1.9, respectively). Paraquat-induced cytotixicity (10-4 M, with a Cl of 22.8 .+-. 1.8) was effectively reduced by catalase 1100 U/ml (Cl 8.0 .+-. 3.2, P < 0.001), superoxide dismutase, 300 U/ml (Cl 17.4, P < 0.05) or .alpha.-tocopherol, 10 .mu.g/ml (Cl 17.8 .+-. 1.6, P < 0.05). Paraquat toxicity (10-3 M) was potentiated in the presence of 95% O2 with an increase in Cl from 31.1 .+-. 1.7 to 36.4 .+-. 2.3 (P < 0.05). Paraquat-induced type 2 cell injury was noted as early as 4 h incubation by EM evidence of swelling of mitochondrial cristae and dispersion of nuclear chromatin. This in vitro model indicated that paraquat-induced type 2 cell injury can be quantified, confirmed by morphologic ultrastructural changes, significantly reduced by antioxidants and potentiated by hyperoxia.