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EXPERIMENTAL INDUCTION OF CHRONIC PULMONARY DISEASE IN GENETICALLY SUSCEPTIBLE RAT MODEL
Citation:
Schladweiler, M., A. D. Ledbetter, K. E. Pinkerton, K. R. Smith, P. S. Gilmour, P A. Evansky, D L. Costa, J. P. Nolan, W P. Watkinson, AND U P. Kodavanti. EXPERIMENTAL INDUCTION OF CHRONIC PULMONARY DISEASE IN GENETICALLY SUSCEPTIBLE RAT MODEL. Presented at American Thoracic Society, Seattle, WA, May 16-21, 2003.
Description:
Experimental induction of chronic pulmonary disease in genetically susceptible rat model. M.C.Schladweiler, BS 1, A.D.Ledbetter 1, K.E.Pinkerton, PhD 2, K.R.Smith, PhD 2, P.S.Gilmour, PhD 1, P.A.Evansky 1, D.L.Costa, ScD 1, W.P.Watkinson, PhD 1, J.P.Nolan 1 and U.P.Kodavanti, PhD 1. 1ETD, NHEERL, ORD, US EPA, RTP, NC and 2UC Davis, Davis, CA.
Common laboratory rodents experience minimal pulmonary inflammatory responses to sulfur dioxide (SO2) or tobacco smoke (TS) exposure, and thus, have not yielded reliable models for the study of COPD pathobiology. We propose that multiple genetic risk factors are essential for rodents to respond similarly to susceptible humans who develop COPD. Thus, we used
Spontaneously Hypertensive (SH) rats, susceptible to oxidative stress, systemic inflammation, and coagulation (known risk factors for COPD), in experimental induction of pulmonary disease.
Male Sprague-Dawley rats (SD) were used as controls. To develop bronchitis, SH and SD rats were exposed nose-only to 0, 250, or 350 ppm SO2, 5 h/dx4d, and to develop emphysema, they
were intratracheally instilled with 0, 400, 800, or 1200 U/kg pancreatic elastase (PE). SH rats were also exposed to TS 80-90 mg/m3, 6 h/d x2-3 d. Pulmonary injury/inflammation, pathology,
mucus secretion, and antioxidants were analyzed. SH rats demonstrated a 37-fold increase in neutrophils, whereas SD developed only a 2-fold increase following SO2 exposure. Mucus
secretion and goblet cell hyperplasia were associated with SO2 in SH but not in SD rats. Similarly, SH but not SD rats mounted marked inflammatory response to TS. TS exposure also
decreased c-reactive protein. Exposure of SH and SD rats to PE caused a dose-dependent lung injury, hemorrhage and neutrophilia. SH mounted greater inflammatory response to PE, SD rats
were more sensitive to hemorrhage. Thus, SH rats, like susceptible humans, may be more responsive to experimental pulmonary disease. This model is being further evaluated for its
similarities to human pathology and genetic factors. (Does not reflect USEPA policy).
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