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ACUTE OZONE-INDUCED INFLAMMATORY GENE EXPRESSION IN THE RAT LUNG IS NOT RELATED TO LEVELS OF ANTIOXIDANTS IN THE LAVAGE FLUID
Citation:
THOMAS, R., M. SCHLADWEILER, A. D. LEDBETTER, G. WALLENBORN, K. M. CRISSMAN, R. H. JASKOT, J. E. RICHARDS, G. E. HATCH, AND U. P. KODAVANTI. ACUTE OZONE-INDUCED INFLAMMATORY GENE EXPRESSION IN THE RAT LUNG IS NOT RELATED TO LEVELS OF ANTIOXIDANTS IN THE LAVAGE FLUID. Presented at 45th Annual Society of Toxicology Meeting 2006, San Diego, CA, March 05 - 09, 2006.
Description:
ABSTRACT BODY: Ozone causes oxidative stress and lung inflammation. We hypothesized that rat strains with or without genetic susceptibility to cardiovascular disease will have different antioxidant levels in alveolar lining, and that ozone induced inflammatory gene expression will be inversely related to the levels of antioxidants. Male 12-15 wk old Sprague Dawley (SD), Wistar (WIS), Wistar Kyoto (WKY), Spontaneously Hypertensive (SH), Stroke-prone SH (SHSP), Heart Failure Hypertensive (SHHF), Diabetic (JCR), and Fawn Hooded Hypertensive (FHH) rats were exposed nose-only to ozone, 0.0, 0.25, 0.5 or 1.0 ppm for 4 h. Bronchoalveolar lavage fluid (BALF) antioxidants were measured at 0 or 20 h later. Lung MIP-2 and TNF-? expression was analyzed using PCR at 0 h in rats exposed to 1 ppm ozone. Base line levels of glutathione (FHH, 0.0; SH, 0.1; WIS, 0.4; SHRSP, 0.5; SD, 1.8; WKY, 1.9; JCR, 6.3 and SHHF, 15.1 ?g/ml) and ascorbate (SH, 1299; SHSP, 2404; WKY, 3446; WIS, 3323; FHH, 3536; SD, 5672; SHHF, 7701; JCR, 8163 ?g/ml) differed in rats. Strains with higher concentration of glutathione also had higher levels of ascorbate. Ozone caused depletion in ascorbate in all strains with smallest effect on SH, as ascorbate levels were lowest in these rats. On the contrary glutathione levels were more variable and were not affected by ozone. Ozone at 1.0 ppm caused marked MIP-2 (WKY, 3.5; SH, 6.0; SHHF 8.0 and SHSP, 10 fold or higher) and TNF- induction (SHHF, 0.4; SHR, 0.8; WKY, 1.0 and SHRSP, 2.5 fold or higher). Gene expression did not necessarily correlate with either the baseline levels or ozone-induced depletion of antioxidants. The relationship between antioxidants and ozone-induced inflammatory potential may not be generalized for all rat strains; other biological variables and genetic differences may play a role in determining susceptibility to ozone (Does not reflect USEPA policy. Supported in part by UNC/EPA CT829471).