Effect of Nitric Oxide and Peroxynitrite in Mucociliary Transport Function of Experimental Otitis Media with Effusion / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Nitric oxide (NO) is generally beneficial but potentially toxic to host. It has been suggested that NO is an important mediator in the pathogenesis of otitis media with effusion. The harmful effect of NO is related with NO-derived intermediates such as peroxynitrite (OONO-). The author investigated the role of NO and peroxynitrite on mucociliary activity in experimental otitis media with effusion. MATERIALS AND METHOD: Otitis media with effusion was induced by injecting lipopolysaccharide (LPS) transtympanically in guinea pigs. In the N(G)-nitro-L-arginine methyl ester (L-NAME) group, L-NAME was additionally injected intratympanically and intramuscularly. Uric acid (UA) group was treated with intraperitoneal injection of UA 3 times. After 24 hours, dye transfer time was measured and temporal bones were taken for histopathologic examination. Expression of peroxynitrite was determined by immunohistochemical stain for 3-nitrotyrosine (3-NT). RESULTS: Transfer time of dye was prolonged in LPS group, whereas it was significantly reduced in L-NAME or UA treatment group. Inflammatory cell infiltration and mucosal edema were less in the treatment groups than LPS group, but it was not statistically significant. 3-NT was expressed intensely in subepithelial layer of LPS group, and decreased to mild to moderate degree in the treatment groups. CONCLUSION: LPS induced mucociliary dysfunction in the middle ear by NO and peroxynitritemediated pathways. This study suggests that inhibition of NO synthesis or scavenging of peroxynitrite may have an adjunctive role in the future treatment of otitis media with effusion.