Ambroxol inhibits peroxynitrite-induced damage of α₁-antiproteinase and free radical production in activated phagocytic cells

The present study examined the effect of ambroxol on toxic action of peroxynitrite and the respiratory burst in activated phagocytic cells. Ambroxol decreased the inactivation or destruction of α₁-antiproteinase induced by peroxynitrite (ONOO^-) or hypochlorous acid (HOCl), which was similar to penicillamine and glutathione and was greater than diclofenac sodium and naproxen sodium. Ambroxol significantly decreased ONOO^--mediated tyrosine nitration and iron plus EDTA-mediated degradation of 2-deoxy-D-ribose. Ambroxol significantly attenuated the production of superoxide, hydrogen peroxide, HOCl, and nitric oxide in fMLP- or IL-1-activated phagocytic cells, while the inhibitory effects of antiinflammatory and thiol compounds were only observed in HOCl production. Ambroxol and antiinflammatory drugs did not show a cytotoxic effect on macrophages. The results suggest that ambroxol protects tissue components against oxidative damage by an action different from antiinflammatory drugs. Ambroxol may interfere with oxidative damage of α₁-antiproteinase through a scavenging action on ONOO^- and HOCl and inhibition of the respiratory burst of phagocytic cells.