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

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Abstract
The 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 did not ffect the toxicity of 1.0 ppm O3. AH2 depletion did not affect phosgene toxicity (at 0.25 pprn and 0.5 ppm. NPSH depletion caused an approximate twofold enhancement in toxicity induced by 10 ppm NO2 and by 0.25 ppm COCl2 but had no effect at other concentrations of these gases and did not affect the toxicity of 0, at any concentration. These results show that protection of lung tissue by AH2 and NPSH is dependent on which toxicant gas is used, and the protective effect is not dose dependent, since in some cases the greatest protection was at the lower concentration.