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Increased susceptibility of hyperthyroid rats to ozone: early events and mechanisms.
Huffman L; Beighley C; Frazer D; McKinney W; Porter D
Toxicologist 2005 Mar; 84(Suppl 1):191
Previous studies have determined that ozone-induced lung damage and inflammation are much greater in hyperthyroid vs. normal rats at 18 hours following exposure. The purpose of the present investigation was to study early events and mechanisms underlying the increased sensitivity to ozone in a hyperthyroid state. Specifically, the degree of lung epithelial cell barrier disruption, extracellular lining fluid antioxidant status, and the release of inflammatory mediators were examined. To create a hyperthyroid condition, mature male Sprague-Dawley rats were implanted with time-release pellets containing thyroxine; control rats received placebo pellets. After 7 days, the animals were exposed to air or ozone (2 ppm, 3 h). Immediately following the end of the exposure, bronchoalveolar lavage (BAL) fluid and cells were harvested. BAL fluid albumin levels and total antioxidant status were examined. In addition, levels of PGE2, MIP-2, MCP-1, and TNF-á were determined in BAL fluid and following ex vivo culture of BAL cells. The results of this study are consistent with the following hypotheses: 1) a marked increase in the permeability of the alveolar-capillary barrier is an early event underlying the increased susceptibility of hyperthyroid rats to ozone, however this does not appear to be due to overall changes in BAL fluid antioxidant potential; 2) early increases in MIP-2, but not PGE2, are involved in the enhanced lung response to ozone in a hyperthyroid state; 3) inflammatory mediator production (i.e., PGE2, MIP-2, MCP-1, and TNF-a) by alveolar macrophages plays a minimal role in the initial responses to ozone in a hyperthyroid state.
Laboratory-animals; Animals; Animal-studies; Lung-disorders; Exposure-levels; Sensitivity-testing; Cell-cultures; Pulmonary-system-disorders; Respiratory-system-disorders; Thyroid-gland; Thyroid-gland-disorders; Endocrine-system; Endocrine-system-disorders
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana
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Content source: National Institute for Occupational Safety and Health Education and Information Division