Asthma, Airway Hyperresponsiveness (AHR), Ovalbumin-Induced
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DOCUMENTS/REFERENCES
BIOLOGICAL INFORMATION
BACKGROUND INFORMATION
Ovalbumin (OVA)-induced model of chronic allergic airway disease (AAD), which presents airway hyperresponsiveness (AHR), is widely used to mimic the features of human asthma. Airway responsiveness of mice to increasing concentrations of aerosolized methacholine (MCh) was measured through a non-invasive whole-body plethysmography system. The main indicator of airflow obstruction, enhanced pause (Penh), which is highly correlated with airway resistance, is assessed in this assay.
ORGANISM
Mouse
ASSAY INFORMATION
ASSAY TYPE
In Vivo
TESTING INFORMATION
PROCEDURE SUMMARY
Groups of 8 male BALB/c mice at 6-7 weeks of age are sensitized with intraperitoneal (IP) injection of ovalbumin (OVA) emulsified in alum (0.1 mL/mouse) on Day 1 and Day 14. The animals are challenged with aerosolized ovalbumin (5% for 30 min) on Days 21, 23 and 25. On Day 26, non-invasive measurements of airway responsiveness are determined using whole body plethysmography and an increase in enhanced pause (Penh) is used as an index of airway obstruction. Responses to inhaled methacholine (10 mg/ml and 30 mg/ml for 5 min) are then measured and calculated as a percentage of respective baseline values. Dexamethasone (3 mg/kg), the standard reference agent, is administered once daily by oral gavage (PO) from Day 21 to Day 26. On Day 26, dexamethasone is given 1 hour before measurements of baseline values. Dosing schedule of test compounds can be similar to dexamethasone or limited to Day 26 before methacholine challenge. Inhibition of methacholine-induced Penh by 50 percent or more indicates possible anti-asthmatic activity. One-way ANOVA followed by Dunnett's test is applied for comparison between vehicle and treatment groups. Activity is considered at p<0.05. Suggested Testing: n=8/group (study design dependent). AHR assessed at an initial dose of 100 mg/kg (PO). Dosing volume at 10 mL/kg.
CRITERIA FOR SIGNIFICANCE
Inhibition of methacholine-induced Penh by ≥50%. One-way ANOVA followed by Dunnett's test is applied for comparison between vehicle and treatment groups.
TURNAROUND TIME
STANDARD
45 Days
CLINICAL RELEVANCE
THERAPEUTIC AREA
Pulmonology
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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