The anti-inflammatory activity of Ebselen but not thiols in experimental alveolitis and bronchiolitis.
This paper describes the effects of the thiol compounds glutathione and N-acetylcysteine and the seleno-organic agent Ebselen on the development of Sephadex-induced lung edema and cell infiltration in the rat. Neither thiol had any effect upon the development of the edema when administered in large, repeated doses. In contrast, when Ebselen was co-administered with the thiols, there was a dose-dependent inhibition of the development of the edema, but lung weights could not be returned to normal values. However, when the thiols were omitted and Ebselen was administered alone, the development of the edema was totally blocked. In addition, in Ebselen-only treated animals there was a selective inhibition of the infiltration of lymphocytes, basophils and eosinophils into the lung lumen without affecting the populations of macrophages and neutrophils. Again, the Ebselen-induced effect was reduced by coadministration of either thiol. These findings are discussed in terms of the potential mechanism of action of Ebselen in vivo and of the possibility of Ebselen being of therapeutic potential in cases of diffuse pulmonary inflammation in humans.
Cotgreave
I A
IA
Department of Toxicology, Karolinska Institutet, Stockholm, Sweden.
Johansson
U
U
Westergren
G
G
Moldéus
P W
PW
Brattsand
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D001988:Bronchiolitis / Q000188:drug therapy*; D002452:Cell Count; D003911:Dextrans / Q000633:toxicity; D005782:Gels / Q000633:toxicity; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds; D011650:Pulmonary Alveoli; D011654:Pulmonary Edema / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D001393:Azoles; D003911:Dextrans; D005782:Gels; D054833:Isoindoles; D016566:Organoselenium Compounds; D013438:Sulfhydryl Compounds; C042986:ebselen; C025614:sephadex; D012643:Selenium