Paraquat-induced injury of type II alveolar cells. An in vitro model of oxidant injury.
Paraquat, a widely used herbicide, causes severe, often fatal lung damage. In vivo studies suggest the alveolar epithelial cells (types I and II) are specific targets of paraquat toxicity. This study used 51Cr-labeled type II cells to demonstrate that paraquat (10-5 M) resulted in type II cell injury in vitro, independent of interacting immune effector agents. With 51Cr release expressed as the cytotoxic index (Cl), type II cell injury was found to accelerate with increasing paraquat concentrations (10(-5) M, 10(-4) M, 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 cytotoxicity (10(-4) M, with a Cl of 22.8 +/- 1.8) was effectively reduced by catalase 1,100 U/ml (Cl 8.0 +/- 3.2, p less than 0.001), superoxide dismutase, 300 U/ml (Cl 17.4 +/- 1.7, p less than 0.05), alpha tocopherol, 10 micrograms/ml (Cl 17.8 +/- 1.6, p less than 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 less than 0.05). Paraquat-induced type II cell injury was noted as early as 4 h incubation by electron microscopic evidence of swelling of mitochondrial cristae and dispersion of nuclear chromatin. Thus, this in vitro model indicates that paraquat-induced type II cell injury can be quantified, confirmed by morphologic ultrastructural changes, significantly reduced by antioxidants, and potentiated by hyperoxia.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D004357:Drug Synergism; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D002860:Chromium Radioisotopes; D014810:Vitamin E; D002374:Catalase; D013482:Superoxide Dismutase; D010269:Paraquat