Effects of Depletion of Ascorbic Acid or Nonprotein Sulfhydryls on the Acute Inhalation Toxicity of Nitrogen Dioxide, Ozone, and Phosgene

AbstractThe effect of depleting lung ascorbic acid (AH2) and nonprotein sulfhydryls (NPSH) on the acute inhalation toxicity of nitrogen dioxide (NO2), ozone (O3), and phosgene (COCl2) was investigated in guinea pigs. The increase in bronchoalveolar lavage (BAL) fluid protein (an indicator of alveolar-capillary damage leading to increased permeability) was measured 16–78 h following a 4-h exposure to the gas in animals deficient in AH2 or NPSH. Gas concentrations were chosen that produced low but significant increases in BAL protein. Lung AH2 was lowered to about 20% of control by feeding rabbit chow for 2 wk. Lung NPSH was lowered to about 50% of control by injecting a mixture of buthionine S, R-sulfoximine (BSO) and diethylmaleate (OEM) (2.7 and 1.2 mmol/kg, respectively). BSO/DEM did not affect the lung concentrations of AH2 or α-tocopherol. AH2 depletion caused a fivefold and a threefold enhancement in the toxicity of 5 ppm and 10 ppm NO2, and a sixfold enhancement in the toxicity of 0.5 ppm O3, but di...