Beta-2-agonists have antioxidant function in vitro. 1. Inhibition of superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl radical.
beta(2)-Agonists are known to have anti-inflammatory efficacy. In this context, beta(2)-agonists are also capable of inhibiting oxidant production of cultured inflammatory cells. As the mechanisms of this function still remain speculative, the purpose of this study was to quantify the efficacy of beta(2)-agonists in vitro to inhibit superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH.) and hypochlorous acid (HOCl). We tested the following antiasthma drugs: ipratropium bromide, salbutamol (salbutamol base), fenoterol (fenoterol hydrobromide), terbutaline (terbutaline sulfate), isoproterenol, prednisolone (prednisolone hydrogensuccinate), beclomethasone (beclomethasone dipropionate) and theophylline (theophylline sulfate). Antioxidant function was quantified by using the following assay systems: O2- (ferricytochrome c + xanthine/xanthine oxidase), H2O2 (phenol red + 5.10(-6) M H2O2), OH. (deoxyribose assay) and HOCI (HOCl/OCl- in luminol-dependent chemiluminescence). At 10(-4) M, the anti-H2O2 and anti-O2- capacity was as follows: salbutamol/terbutaline < fenoterol < isoproterenol. 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 had no antioxidant effect. These results demonstrate the different redox potentials of different phenol types within the molecular structure of the beta(2)-agonists. The good antioxidative function of isoproterenol is related to ortho formation of the phenol ring, whereas fenoterol has tow phenol rings which can be oxidized. A direct oxidant scavenger function may explain the ability of beta(2)-agonists to reduce the oxidant production of inflammatory cells in vitro.
Gillissen
A
A
Department of Internal Medicine, University Hospital Bergmannsheil, Bochum, Germany.
Jaworska
M
M
Schärling
B
B
van Zwoll
D
D
Schultze-Werninghaus
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D018927:Anti-Asthmatic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D003124:Colorimetry; D016166:Free Radical Scavengers; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors*; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors*; D006997:Hypochlorous Acid / Q000037:antagonists & inhibitors*; D008163:Luminescent Measurements; D010084:Oxidation-Reduction; D013053:Spectrophotometry; D013481:Superoxides / Q000037:antagonists & inhibitors*
D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D000975:Antioxidants; D016166:Free Radical Scavengers; D013481:Superoxides; D017665:Hydroxyl Radical; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide