A. Gillissen et al., BETA-2-AGONISTS HAVE ANTIOXIDANT FUNCTION IN-VITRO .1. INHIBITION OF SUPEROXIDE ANION, HYDROGEN-PEROXIDE, HYPOCHLOROUS ACID AND HYDROXYL RADICAL, Respiration, 64(1), 1997, pp. 16-22
beta(2)-Agonists are known to have anti-inflammatory efficacy. In this
context, beta(2)-agonists are also capable of inhibiting oxidant prod
uction of cultured inflammatory cells. As the mechanisms of this funct
ion still remain speculative, the purpose of this study was to quantif
y the efficacy of beta(2)-agonists in vitro to inhibit superoxide anio
n (O-2(-)), hydrogen peroxide (H2O2), hydroxyl radical (OH') and hypoc
hlorous acid (HOCl). We tested the following antiasthma drugs: ipratro
pium bromide, salbutamol (salbutamol base), fenoterol (fenoterol hydro
bromide), terbutaline (terbutaline sulfate), isoproterenol, prednisolo
ne (prednisolone hydrogensuccinate), beclomethasone (beclomethasone di
propionate) and theophylline (theophylline sulfate). Antioxidant funct
ion was quantified by using the following assay systems: O-2(-) (ferri
cytochrome c + xan thine/xanthine oxidase), H2O2 (phenol red + 5 . 10(
-6) M H2O2), OH' (deoxyribose assay) and HOCl (HOCl/OCl- in luminol-de
pendent chemiluminescence). At 10(-4) M, the anti-H2O2 and anti-O-2(-)
capacity was as follows: salbutamol/terbutaline <fenoterol <isoproter
enol, All beta(2)-agonists ( 10(-4) M) tested reduced HOCl activity by
>50% (p < 0.01). In contrast, moderate OH' reduction (10-30%) by the
beta(2)-agonists is regarded as an nonspecific effect, due to the high
concentrations needed (10(-3) M). Corticosteroids and theophylline ha
d no antioxidant effect. These results demonstrate the different redox
potentials of different phenol types within the molecular structure o
f the beta(2)-agonists. The good antioxidative function of isoproteren
ol is related to ortho formation of the phenol ring, whereas fenoterol
has two phenol rings which can be oxidized. A direct oxidant scavenge
r function may explain the ability of Pz-agonists to reduce the oxidan
t production of inflammatory cells in vitro.