Nitric Oxide and Reactive Oxygen Species Production Causes Progressive Damage in Rats after Cessation of Silica Inhalation
| Autor: | Dale W. Porter, Jeffery McLaurin, Kurt Brumbaugh, Vincent Castranova, Christoper M. Beighley, Lyndell Millecchia, Alexander W. Teass, Dawn Ramsey, Amir Khan, Victor A. Robinson, Patsy Willard |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Pathology medicine.medical_specialty Time Factors Silicosis Nitric Oxide Synthase Type II Air Pollutants Occupational Nitric Oxide Toxicology medicine.disease_cause Nitric oxide chemistry.chemical_compound Fibrosis Internal medicine Administration Inhalation Macrophages Alveolar medicine Animals Lung Inhalation exposure chemistry.chemical_classification Inhalation Exposure Reactive oxygen species biology Inhalation Chemistry respiratory system Silicon Dioxide medicine.disease Rats Inbred F344 Rats Specific Pathogen-Free Organisms Nitric oxide synthase Disease Models Animal Endocrinology biology.protein Alveolar macrophage Reactive Oxygen Species Bronchoalveolar Lavage Fluid Oxidative stress |
| Zdroj: | Toxicological Sciences. 90:188-197 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfj075 |
| Popis: | 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 relationship 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 magnitude during the postexposure period, and (3) the presence of silica particle(s) in an alveolar macrophage (AM) was highly associated with inducible nitric oxide synthase (iNOS) protein. These data indicate that, even after silica exposure has ended, and despite declining silica lung burden, silica-induced pulmonary NO and ROS production increases, thus producing a more severe oxidative stress. A quantitative association between silica and expression of iNOS protein in AMs was also determined, which adds to our previous observation that iNOS and NO-mediated damage are associated anatomically with silica-induced pathological lesions. Future studies will be needed to determine whether the progressive oxidative stress, and iNOS activation and NO production, is a direct result of silica lung burden or a consequence of silica-induced biochemical mediators. |
| Databáze: | OpenAIRE |
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