Ebselen decreases ozone-induced pulmonary inflammation in rats.
We studied the effects of ebselen on rat lung inflammatory responses against ozone exposure. Rats were treated with ebselen every 12 h from 1 h before a single 4-h exposure to 2 ppm ozone. Treatment with ebselen (10 mg/kg) significantly decreased pulmonary inflammation as indicated by the albumin concentration and the number of neutrophils in the bronchoalveolar lavage fluid 18 h after the ozone exposure. Although treatment with ebselen did not alter the macrophage expression of inducible nitric oxide synthase after the ozone exposure, it did markedly inhibit the nitration reaction of tyrosine residues, suggesting that ebselen scavenges peroxynitrite during ozone-induced pulmonary inflammation. Treatment with ebselen also enhanced the pulmonary expression of both copper, zinc, and manganous superoxide dismutases at the same time point. These enzymes may also contribute to a decrease in the formation of peroxynitrite by lowering the concentration of superoxide. Thus, ebselen represents a useful compound for protecting against certain acute lung injuries by modulating the oxidant-related inflammatory process.
Ishii
Y
Y
Department of Respiratory Medicine, University of Tsukuba, 1-1-1 Ten-nohdai, Tsukuba, Ibaraki 305, Japan.
Hashimoto
K
K
Hirano
K
K
Morishima
Y
Y
Mochizuki
M
M
Masuyama
K
K
Nomura
A
A
Sakamoto
T
T
Uchida
Y
Y
Sagai
M
M
Sekizawa
K
K
D000208:Acute Disease; D000418:Albumins / Q000032:analysis; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001393:Azoles / Q000627:therapeutic use*; D015152:Blotting, Northern / Q000379:methods; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004353:Drug Evaluation, Preclinical; D007150:Immunohistochemistry; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds / Q000627:therapeutic use*; D010126:Ozone / Q000009:adverse effects*; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000418:Albumins; D000975:Antioxidants; D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen; D010126:Ozone