Glucocorticoids reduce nitric oxide concentration in middle ear effusion from lipopolysaccharide induced otitis media
Received 4 November 2009; received in revised form 8 January 2010; accepted 12 January 2010.
Abstract
Objective
Otitis media with effusion (OME) is a common childhood disease that is characterized by an accumulation of fluid in the middle ear. Chronic OME can also lead to sensorineural hearing loss (SNHL). Nitric oxide (NO), an inflammatory mediator (IM) of OME, is a free radical known to regulate cell proliferation, cell death, and angiogenesis. Previous studies have shown that nitric oxide may cause SNHL through outer hair cell (OHC) cytotoxicity. This experiment was designed to determine whether glucocorticoids, dexamethasone, fluticasone propionate, or rimexolone, can reduce the concentration of NO in middle ear effusion (MEE).
Methods
Fifty-three chinchillas were divided into 7 groups, vehicle vs. each glucocorticoid at 0.1% and 1.0% concentrations. Due to anesthesia complications, N ranged from 6 to 9 per group. Two hundred microlitres of each test article was injected into the bullae of each animal. Two hours later, lipopolysaccharide (LPS) (0.3mg in solution) was added. Test articles were re-administered at 24 and 48h post-LPS induction. After 96h, animals were euthanized and the MEE was collected.
Results
All three glucocorticoids numerically reduced NO concentration in the middle ear when administered at 0.1%, but only FP showed a significant reduction. At 1.0% concentrations, all 3 steroids significantly reduced NO concentration.
Conclusion
This study suggests that glucocorticoid treatment reduces NO concentration in the MEE and may protect the ear from the SNHL caused by NO.
aDivision of Otolaryngology-Head & Neck Surgery, Loma Linda University School of Medicine and Jerry L. Pettis Memorial Veterans Affairs Medical Center, Loma Linda, CA 92354, United States
bAlcon Research, Ltd., Fort Worth, TX, United States
ABSTRACT