Document Detail

The spontaneously hypertensive rat: an experimental model of sulfur dioxide-induced airways disease.
MedLine Citation:
PMID:  16929007     Owner:  NLM     Status:  MEDLINE    
Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction, inflammation, and mucus hypersecretion, features that are common in bronchitis, emphysema, and often asthma. However, current rodent models do not reflect this human disease. Because genetically predisposed spontaneously hypertensive (SH) rats display phenotypes such as systemic inflammation, hypercoagulation, oxidative stress, and suppressed immune function that are also apparent in COPD patients, we hypothesized that SH rat may offer a better model of experimental bronchitis. We, therefore, exposed SH and commonly used Sprague Dawley (SD) rats (male, 13- to 15-weeks old) to 0, 250, or 350 ppm sulfur dioxide (SO(2)), 5 h/day for 4 consecutive days to induce airway injury. SO(2) caused dose-dependent changes in breathing parameters in both strains with SH rats being slightly more affected than SD rats. Increases in bronchoalveolar lavage fluid (BALF) total cells and neutrophilic inflammation were dose dependent and significantly greater in SH than in SD rats. The recovery was incomplete at 4 days following SO(2) exposure in SH rats. Pulmonary protein leakage was modest in either strain, but lactate dehydrogenase and N-acetyl glucosaminidase activity were increased in BALF of SH rats. Airway pathology and morphometric evaluation of mucin demonstrated significantly greater impact of SO(2) in SH than in SD rats. Baseline differences in lung gene expression pattern suggested marked immune dysregulation, oxidative stress, impairment of cell signaling, and fatty acid metabolism in SH rats. SO(2) effects on these genes were more pronounced in SH than in SD rats. Thus, SO(2) exposure in SH rats may yield a relevant experimental model of bronchitis.
Urmila P Kodavanti; Mette C Schladweiler; Allen D Ledbetter; Roselia Villalobos Ortuno; Marie Suffia; Paul Evansky; Judy H Richards; Richard H Jaskot; Ronald Thomas; Edward Karoly; Yuh-Chin T Huang; Daniel L Costa; Peter S Gilmour; Kent E Pinkerton
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Publication Detail:
Type:  Journal Article     Date:  2006-08-23
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  94     ISSN:  1096-6080     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-05     Completed Date:  2007-03-13     Revised Date:  2010-09-17    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  193-205     Citation Subset:  IM    
Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711, USA.
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MeSH Terms
Acetylglucosaminidase / metabolism
Administration, Inhalation
Bronchitis / chemically induced,  metabolism*,  physiopathology
Bronchoalveolar Lavage Fluid / cytology
Chemokine CXCL2
Chemokines, CXC / genetics
Cluster Analysis
Disease Models, Animal
Dose-Response Relationship, Drug
Gene Expression Profiling / methods
Gene Expression Regulation / drug effects
L-Lactate Dehydrogenase / metabolism
Mucus / secretion
Oligonucleotide Array Sequence Analysis / methods
RNA, Messenger / genetics,  metabolism
Rats, Inbred SHR / genetics,  metabolism*
Rats, Sprague-Dawley
Respiratory Mechanics / drug effects
Species Specificity
Sulfur Dioxide / administration & dosage,  toxicity*
Time Factors
Tumor Necrosis Factor-alpha / genetics
Weight Loss / drug effects
Reg. No./Substance:
0/Chemokine CXCL2; 0/Chemokines, CXC; 0/Cxcl2 protein, rat; 0/RNA, Messenger; 0/Tumor Necrosis Factor-alpha; 7446-09-5/Sulfur Dioxide; EC Dehydrogenase; EC

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