Gillissen A, Jaworska M, Schärling B, van Zwoll D, Schultze-Werninghaus G
Department of Internal Medicine, University Hospital Bergmannsheil, Bochum, Germany.
Respiration. 1997;64(1):16-22. doi: 10.1159/000196637.
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.
已知β₂激动剂具有抗炎功效。在此背景下，β₂激动剂还能够抑制培养的炎症细胞产生氧化剂。由于该功能的机制仍属推测，本研究的目的是在体外定量β₂激动剂抑制超氧阴离子（O₂⁻）、过氧化氢（H₂O₂）、羟自由基（OH·）和次氯酸（HOCl）的功效。我们测试了以下抗哮喘药物：异丙托溴铵、沙丁胺醇（沙丁胺醇碱）、非诺特罗（氢溴酸非诺特罗）、特布他林（硫酸特布他林）、异丙肾上腺素、泼尼松龙（氢化琥珀酸泼尼松龙）、倍氯米松（二丙酸倍氯米松）和茶碱（硫酸茶碱）。通过使用以下检测系统对抗氧化功能进行定量：O₂⁻（高铁细胞色素c + 黄嘌呤/黄嘌呤氧化酶）、H₂O₂（酚红 + 5×10⁻⁶ M H₂O₂）、OH·（脱氧核糖检测法）和HOCl（鲁米诺依赖性化学发光中的HOCl/OCl⁻）。在10⁻⁴ M时，抗H₂O₂和抗O₂⁻能力如下：沙丁胺醇/特布他林＜非诺特罗＜异丙肾上腺素。所有测试的β₂激动剂（10⁻⁴ M）均可使HOCl活性降低＞50%（p＜0.01）。相比之下，β₂激动剂使OH·适度降低（10% - 30%）被视为非特异性效应，因为所需浓度较高（10⁻³ M）。皮质类固醇和茶碱没有抗氧化作用。这些结果表明β₂激动剂分子结构中不同酚类的氧化还原电位不同。异丙肾上腺素良好的抗氧化功能与酚环的邻位形成有关，而非诺特罗有两个可被氧化的酚环。直接的氧化剂清除功能可能解释了β₂激动剂在体外降低炎症细胞氧化剂产生的能力。
