OXIDANT SCAVENGER FUNCTION OF AMBROXOL IN-VITRO - A COMPARISON WITH N-ACETYLCYSTEINE

Highly reactive oxygen metabolites play an important role in inflammat ory processes in the lung. Ambroxol -dibromo-N-[trans-4-hydroxycyclohe xyl]benzylamine) has been shown to reduce oxidant-mediated cell damage . However, the mechanism of this effect remains unclear. In order to e valuate oxidant scavenger function increasing concentrations of ambrox ol (0-10(-3) mol/l) were compared with equimolar concentrations of N-a cetylcysteine (NAG) and glutathione (GSH) in vitro to reduce OH. (hydr oxyl radical), HOCl (hypochlorous acid), O-2(-) (superoxide anion) and H2O2 (hydrogen peroxide). OH. was measured spectrophotometrically (de oxyribose assay); O-2(-) (xanthine/x-oxidase), H2O2 and HOCl (HOCI/OCl -) were determined by chemiluminescence. Ambroxol, NAC and reduced GSH scavenged OH. significantly at 10(-3) mol/l, while HOCl was inhibited at concentrations greater than or equal to 10(-4) mol/l completely (P <0.01). NAC and GSH had no anti-O-2(-) function, while ambroxol (10(-4 ) mol/l) reduced O-2(-) by 14.3+/-6.7%. In contrast, GSH and NAC scave nged H2O2 at >10(-6) mol/l (P<0.01), while ambroxol had no anti-H2O2 e ffect. Our data demonstrate direct oxidant-reducing capabilities of am broxol, which may be directly related to the aromatic moiety of the mo lecule. However, high concentrations (micromolar concentrations) are n eeded. Due to differences in direct oxidant scavenger function, a comb ination of ambroxol and NAC could be beneficial in antioxidant therapy .