Effects of Ebselen on Ozone-Induced Nasal Mucosal Inflammation in Mice

Yoo, Mun Sik; Jin, Yong De; Park, Young Kyu; Min, In Kyu; Park, Seok Won; Rha, Ki Sang; Park, Chan Il

Abstract

BACKGROUND AND OBJECTIVES
Although the mechanism of ozone-induced airway inflammation and hyperresponsiveness is largely unknown, NO and peroxynitrite has been suggested to be associated with it. Ebselen, a seleno-organic compound, is known to inhibit the production of superoxide, iNOS-related NO, and their combined product, peroxynitrite. The purpose of this study is to investigate whether ebselen suppress ozone-induced nasal inflammation and whether ebselen inhibit the production of NO and peroxynitrite in nasal mucosa. SUBJECTS AND METHOD: Thirty-six BALB/c mice were divided into three groups: control group, ozone exposure group, and ozone+ebselen treated group. In the ozone exposure group, mice were exposed to 1 ppm ozone for 8 hours a day for 3 consecutive days. In the ebselen treated group, the ebselen (32.5 mg/kg) solution was injected intraperitoneally 1 hour before and 3 hours after the ozone exposure. At 18 hours of the last ozone exposure, Evans blue was infused via tail vein in 6 animals of each group. Mice were sacrificed five minutes later and nasal mucosa was obtained to measure the amount of extravasated Evans blue dye. From the remaining 6 animals in each group, nasal lavage fluid (NLF) was obtained to measure the concentration of albumin and the number of neutrophils. After lavage fluid was obtained, nasal mucosa was taken for immunohistochemical staining against iNOS and nitrotyrosine usng the ABC method. RESULTS: Extravasation of Evans blue was significantly increased in the ozone exposure group, but it was significantly decreased in the ebselen treated group. Albumin concentration in NLF showed a tendency to increase in the ozone exposure group and a tendency to decrease in the ebselen treated group when compared with the ozone exposure group. The number of neutrophils was significantly increased in the ozone exposure group and was decreased more in the ebselen treated group than in the ozone exposure group. Immunoreactivity to iNOS and nitrotyrosine was strongly expressed in nasal mucosa of the ozone exposure group. However, it was nearly abolished by the treatment with ebselen. CONCLUSIONS: These results may suggest that ebselen can be applied as a useful therapeutic agent for airway diseases by modulating the oxidant-related inflammatory process.