Synergistic interaction of ozone and respirable aerosols on rat lungs. IV. Protection by quenchers of reactive oxygen species.

In previous studies we have shown interactions between ozone and acidic respirable aerosols as evaluated by sensitive biochemical and quantitative morphological endpoints. In the present paper we have attempted to test the hypothesis that active oxygen species might play a role in lung damage caused by ozone +/- sulfuric acid aerosol. Rats were administered various scavengers of active oxygen species via the intraperitoneal (i.p.) route before and during exposure to 0.12, 0.20, or 0.64 ppm of ozone +/- 0.04, 0.1, 0.2, 0.5, or 1.0 mg/m3 of sulfuric acid aerosol. Vitamin E, a lipid-soluble free radical scavenger, beta-carotene (the precursor of vitamin A), a singlet oxygen scavenger, and dimethylthiourea, a hydrogen peroxide scavenger, were tested. Dimethylthiourea at doses of 50-500 mg/kg per day was able to protect rats from the effects of ozone, suggesting a role for hydrogen peroxide in ozone-induced lung damage in vivo. Neither vitamin E nor beta-carotene at 100 mg/kg doses had any protective activity in our experiments, despite documentation of increased lung content of the scavengers in animals receiving these agents. These results suggest that water solubility may play a role in the efficacy of the scavenging agents under our exposure protocols. We conclude that: (1) hydrogen peroxide may be involved in ozone-induced lung damage; and (2) that lung injury by ozone and by ozone + sulfuric acid aerosol may share common pathways.