Chronic Obstructive Pulmonary Disease (COPD), Elastase-Induced
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DOCUMENTS/REFERENCES
BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
Chronic obstructive pulmonary disease (COPD) is a serious health problem with high morbidity and mortality rates. It is characterized by lung parenchyma destruction, emphysema, and chronic lung inflammation. The pathophysiology of airways in COPD involves oxidative stress, neutrophilic airway inflammation, and protease–anti-protease imbalance. Porcine pancreatic elastase (PPE) is a protease that can induce the breakdown of alveolar tissue and emphysema and has been commonly used as an animal model for COPD and to evaluate the therapeutic efficacy of drug candidates.
ORGANISM
Mouse
ASSAY INFORMATION
ASSAY TYPE
In Vivo
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 8 male BALB/c mice at the age of 7-8 weeks old are used. The animals are anesthetized with isoflurane and receive intratracheal instillation (IT) of porcine pancreatic elastase (PPE, 1.2 U/20 μL/mouse) on Days 0, 7, 14, and 21 and E. Coli lipopolysaccharide (LPS, 7 μg/20 μL/mouse) on Days 4, 11, 18 and 25. Sham control receives the same volume of saline intratracheally. Vehicle and test articles will be administered by oral gavage once daily starting immediately post-PPE administration through Day 27. Body weight will be recorded 3 times per week during the study period. On Day 28, mice are anesthetized by pentobarbital (80 mg/kg, i.p.), 0.25 mL of phosphate-buffered saline (PBS) is administered twice through a tracheal cannula after which about 0.3 mL of bronchoalveolar lavage fluid (BALF) is obtained. Total cell counts and differential cell counts in BALF are determined by an automatic hematology analyzer. Lung tissues are formalin-fixed, paraffin-embedded, and stained by hematoxylin and eosin (H&E) method for histopathology. The mean linear intercept (Lm) can be calculated.
CRITERIA FOR SIGNIFICANCE
ANOVA and Dunnett’s test are used to ascertain difference between vehicle control and treated mice. Significance is set at p<0.05 level.
TURNAROUND TIME
STANDARD
50 Days
CLINICAL RELEVANCE
THERAPEUTIC AREA
Inflammation/Allergy
ADDITIONAL INFORMATION
BRAND
PDS
TESTING LOCATION
Taiwan - Taipei
OTHER INFORMATION
We will readily accommodate client-specified alterations. These studies are performed at our AAALAC accredited BSL-2 laboratory in Taipei, Taiwan. All aspects of this work are performed in general accordance with the Guide for the Care and Use of laboratory animals (National Academy Press, Washington, DC, 2011). The study protocol was approved by the Pharmacology Discovery Services IACUC and is performed with the oversight of veterinarians to assure the humane treatment of laboratory animals.
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