EPA Science Inventory

PULMONARY AND SYSTEMIC EFFECTS OF FOUR-WEEK DIESEL INHALATION IN HEALTHY AHD HYPERTENSIVE RATS

Citation:

GOTTIPOLU, R., M. SCHLADWEILER, A. NYSKA, G. WALLENBORN, A. D. LEDBETTER, D. MALARKEY, D. W. WINSETT, J. E. RICHARDS, Q. T. KRANTZ, M. I. GILMOUR, R. THOMAS, R. H. JASKOT, AND U. P. KODAVANTI. PULMONARY AND SYSTEMIC EFFECTS OF FOUR-WEEK DIESEL INHALATION IN HEALTHY AHD HYPERTENSIVE RATS. Presented at Society of Toxicology Annual Meeting, Charlotte, NC, March 25 - 29, 2007.

Description:

Diesel exhaust (DE) comprises a significant fraction of near road ambient particulate matter (PM). Exacerbated cardiac and pulmonary complications are noted in individuals residing near roadways. We examined pulmonary and systemic effects of diesel exhaust (DE) in healthy and hypertensive rats to investigate potential mechanisms and susceptibility. Male Wistar Kyoto (WKY) and Spontaneously Hypertensive (SH) rats (12-14 weeks age) were exposed whole body to air or freshly generated DE (gas plus particles) at 0.5 and 2.0 mg/m3x6h/dx5d/wkx4 wks. Lung injury and inflammation were assessed by histopathology and bronchoalveolar lavage fluid (BALF) analysis while systemic effects were assessed by plasma cytokines and hematological measurements. DE caused concentration-dependent increases in BALF neutrophils in both strains but no significant net accumulation of macrophages, despite the presence of particle-laden macrophages. Pulmonary protein leakage was modest but the activity of a cell injury marker, ¿-glutamyl transferase was significantly increased in both strains. Lung pathology was characterized by thickening of alveolar septa, presence of alveolar pigmented histiocytes, interstitial inflammation and focal mast cell aggregation. Plasma cytokines, fibrinogen, and hematological parameters were not altered except for modest increases in white blood cells of SH and WKY and hematocrit values of SH rats exposed to DE. Noted inherent strain differences were likely due to presence of cardivascular disease in SH rats; however, no striking exposure-related differences were apparent in any of the measured markers. These data demonstrate that 4-wk inhalation of rats to DE causes pulmonary inflammation and pathology but only modest systemic effects as noted in healthy and genetically hypertensive rats. (This abstract does not reflect US EPA policy. Supported in part by UNC/EPA CT829471 and NRC Research Associateship Award at NHEERL, EPA).

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Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Start Date: 03/26/2007
Completion Date: 03/26/2007
Record Last Revised: 04/04/2007
Record Created: 10/04/2006
Record Released: 10/04/2006
Record ID: 159586

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB

EXPERIMENTAL TOXICOLOGY DIVISION

PULMONARY TOXICOLOGY BRANCH