The effect of lung alpha-tocopherol content on the acute toxicity of nitrogen dioxide.
The effect of lung vitamin E content on early direct damage to lung by NO2 was studied by exposing three groups of rats differing in lung vitamin E content to 0, 10, 20, 30, and 40 ppm NO2 for 4 hr. Lung vitamin E contents of 3.24, 17.4, and 87.7 micrograms/lung were obtained by maintaining animals on semipurified diets containing 0, 10, or 1000 mg/kg of d-alpha-tocopherol acetate. Animals were sacrificed immediately after the 4-hr exposure and lung damage was assessed by assaying the lung lavage content of protein, sialic acid, lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (GDH), acid phosphatase (AP), and aryl sulfatase (AS), all of which increase in lavage fluid in a concentration-dependent manner over the range of NO2 concentrations used. Increases in lavagable protein, sialic acid, AP, and AS were not affected by the different vitamin E contents, while the increases in LDH, MDH, and GDH were significantly attenuated in the 1000-mg/kg diet group relative to the 0- and 10-mg/kg diet groups. Lipid peroxidation was not detectable in NO2-exposed lungs by either conjugated diene measurement or thiobarbituric-acid-reactive materials, with the exception of a slight increase in thiobarbituric-acid-reactive material in free cells. These results suggest two mechanisms of NO2 damage to lung. The attenuation of the appearance of some lavage parameters by high vitamin E is consistent with lipid peroxidation as a necessary event in the damage responsible for their appearance, although the lack of change in indicators of lipid peroxidation in the whole lung suggests that peroxidation occurs to only a very limited extent. The lavage parameters which are unaffected by lung vitamin E content apparently appear in airways as a result of events not involving lipid peroxidation.
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001273:Atmosphere Exposure Chambers; D004347:Drug Interactions; D005231:Fatty Acids, Unsaturated / Q000032:analysis; D008054:Lipid Peroxides / Q000378:metabolism; D008168:Lung / Q000032:analysis / Q000187:drug effects*; D008297:Male; D009585:Nitrogen Dioxide; D051381:Rats; D014810:Vitamin E / Q000032:analysis / Q000097:blood / Q000494:pharmacology*
D005231:Fatty Acids, Unsaturated; D008054:Lipid Peroxides; D014810:Vitamin E; D009585:Nitrogen Dioxide