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 /sup 51/Cr-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 /sup 51/Cr 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.
- Research Organization:
- Division of Thoracic Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota
- OSTI ID:
- 6626883
- Journal Information:
- Am. Rev. Respir. Dis.; (United States), Vol. 129:6
- Country of Publication:
- United States
- Language:
- English
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EPITHELIUM
ULTRASTRUCTURAL CHANGES
HERBICIDES
TOXICITY
CHROMIUM 51
ELECTRON MICROSCOPY
INJURIES
LUNGS
TRACER TECHNIQUES
ANIMAL TISSUES
BETA DECAY RADIOISOTOPES
BODY
CHROMIUM ISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
MICROSCOPY
MORPHOLOGICAL CHANGES
NUCLEI
ORGANS
PESTICIDES
RADIOISOTOPES
RESPIRATORY SYSTEM
TISSUES
550901* - Pathology- Tracer Techniques