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RESPIRATORY EFFECTS OF INHALED METAL-RICH PARTICULATE MATTER (PM) IN RATS: INFLUENCE OF SYSTEMIC ANTIOXIDANT DEPLETION
Citation:
DYE, J. A., A. D. LEDBETTER, R. SLADE, J. E. RICHARDS, C. HAYES, AND D. W. WINSETT. RESPIRATORY EFFECTS OF INHALED METAL-RICH PARTICULATE MATTER (PM) IN RATS: INFLUENCE OF SYSTEMIC ANTIOXIDANT DEPLETION. Presented at ATS Annual Meeting, San Diego, CA, May 19 - 24, 2006.
Description:
Metal-mediated generation of reactive oxygen species and resultant oxidative stress has been implicated in the pathogenesis of emission-source PM toxicity. We hypothesized that inducing an antioxidant deficit prior to inhalation of metal-rich PM would worsen adverse health outcome. 10-wk CD rats were exposed to air or nose-only PM from an oil-fired furnace (5h/d x 2d; 15.5 mg/M^3). A subset of rats received buthionine sulfoximine (BSO; 2.5 mMol/kg IP q 12h x 4) to deplete glutathione (GSH). Airway responsiveness (AR) was assessed after day 2; rats were euthanized 20h later and evaluated for lung / bronchoalveolar lavage fluid (BALF) antioxidant levels, lung injury/inflammation, and nasal gene expression using RT PCR. Relative to air:sal controls, BALF from PM:sal-exposed rats had significantly increased total antioxidant capacity (TAC) and GGT levels, mildly increased NAG and TP, and numerous PM-ladened alveolar macrophages but minimal inflammatory cell influx. Lung GSH levels were decreased 50% in air:BSO-exposed rats although BALF TAC was increased. PM-BSO-treated rats had similar GSH decrements, yet the TAC decreased despite increased GGT levels. BSO treatment had negligible effects on BALF cell content. Neither saline- nor BSO-treated rats had increased AR after PM exposure. RT PCR of nasal RNA revealed that, relative to air:sal controls, PM:sal-exposure resulted in increased MIP-2, RANTES, and NGF-¿ gene expression. BSO treatment did not affect these changes. Thus, nasal gene assessment appears to be a sensitive method to detect epithelial responses to inhaled PM. Despite decrements in lung GSH, these healthy outbred rats failed to develop significant PM-induced lung injury or inflammation. Changes in BALF TAC and GGT levels suggest that rats were capable of eliciting protective antioxidant responses at the lung surface. (Abstract does not reflect USEPA policy.)