Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica

Our laboratory has previously reported results from a rat silica inhalation study which determined that, even after silica exposure ended, pulmonary inflammation and damage progressed with subsequent fibrosis development. In the present study, the re-lationship between silica exposure, nitric oxide (NO) and reactive oxygen species (ROS) production, and the resultant pulmonary damage is investigated in this model. Rats were exposed to silica (15 mg/m3, 6 h/day) for either 20, 40, or 60 days. A portion of the rats from each exposure were sacrificed at 0 days postexposure, while another portion was maintained without further exposure for 36 days to examine recovery or progression. The major findings of this study are: (1) silica-exposed rat lungs were in a state of oxidative stress, the severity of which increased during the postexposure period, (2) silica-exposed rats had significant increase in lung NO production which increased in magnitud