β-lapachone reduces endotoxin-induced macrophage activation and lung edema and mortality
Journal
American Journal of Respiratory and Critical Care Medicine
Journal Volume
168
Journal Issue
1
Pages
85-91
Date Issued
2003
Author(s)
Abstract
β-Lapachone, a 1,2-naphthoquinone, is a novel chemotherapeutic agent. It has been shown to be capable of suppressing inducible nitric oxide synthase expression and function in rat alveolar macrophages. The authors further performed experiments to examine the molecular mechanism of β-lapachone on LPS-induced responses in rat alveolar macrophages and to evaluate its in vivo antiinflammatory effect. A significant increase in nitrite production and inducible nitric oxide synthase expression was elicited in macrophages treated with LPS that was inhibited by coincubation with β-lapachone. β-Lapachone could also inhibit the production of tumor necrosis factor-α induced by LPS. LPS induces protein tyrosine phosphorylation and nuclear factor-κB binding activity by gel mobility shift assay in macrophages. These events were significantly inhibited by β-lapachone. Furthermore, β-lapachone in vivo protected against the induction of lung edema, lung-inducible nitric oxide synthase protein expression and nuclear factor-κB activation, lethality, and increased plasma nitrite and serum tumor necrosis factor-α levels induced by LPS. These results indrcate that β-lapachone suppresses inducible nitric oxide synthase induction and tumor necrosis factor-α production mediated by the inhibition of protein tyrosine phosphorylation and nuclear factor-κB activation caused by LPS. This results in a beneficial effect in an animal model of sepsis.
SDGs
Type
journal article