Braga P C, Lattuada N, Greco V, Sibilia V, Falchi M, Bianchi T, Dal Sasso M
Department of Medical Biotechnology and Translational Medicine, School of Medicine, University of Milan, Milan, Italy.
AVIS Comunale di Milano, Ospedale Niguarda, Milano, Italy.
Drug Res (Stuttg). 2015 May;65(5):244-51. doi: 10.1055/s-0034-1377002. Epub 2014 Jun 11.
A new diclofenac salt called diclofenac-choline (DC) has recently been proposed for the symptomatic treatment of oropharyngeal inflammatory processes and pain because its greater water solubility allows the use of high concentrations, which are useful when the contact time between the drug and the oropharyngeal mucosa is brief, as in the case of mouthwashes or spray formulations. The antioxidant activity of DC has not yet been investigated, and so the aim was to use luminol-amplified-chemiluminescence (LACL) to verify whether various concentrations of DC (1.48, 0.74 and 0.37 mg/mL for incubation times of 2, 4 and 8 min) interfere with oxygen and nitrogen radicals during the course of human neutrophils respiratory bursts; electron paramagnetic resonance (EPR) spectroscopy was used to investigate its direct antiradical (scavenger) activity. The EPR findings showed that DC has concentration-dependent scavenging activity against the ABTS, the DPPH, and the hydroxyl radicals, but no activity on superoxide anion, as has been previously reported in the case of other NSAIDs. LACL revealed an inhibitory effect that was statistically significant after only 2 min of incubation, and similar after 4 and 8 min. The effects on the peroxynitrite radical paralleled those observed in the previous test. High concentrations and short incubation times showed that there is no interference on PMN viability, and so the inhibitory findings must be attributed to the effect of the drug. The anti-inflammatory effects of DC cannot be attributed solely to the inhibition of prostaglandin synthesis, but its effects on free radicals and neutrophil bursts suggest that they may contribute to its final therapeutic effect.
一种名为双氯芬酸胆碱（DC）的新型双氯芬酸盐最近被提议用于口咽炎症过程和疼痛的对症治疗，因为其更高的水溶性允许使用高浓度，这在药物与口咽黏膜接触时间较短的情况下很有用，如漱口水或喷雾制剂的情况。DC的抗氧化活性尚未得到研究，因此目的是使用鲁米诺放大化学发光（LACL）来验证不同浓度的DC（分别为1.48、0.74和0.37mg/mL，孵育时间为2、4和8分钟）在人类中性粒细胞呼吸爆发过程中是否会干扰氧自由基和氮自由基；电子顺磁共振（EPR）光谱用于研究其直接抗自由基（清除剂）活性。EPR结果表明，DC对ABTS、DPPH和羟基自由基具有浓度依赖性清除活性，但对超氧阴离子没有活性，这与之前其他非甾体抗炎药的情况一致。LACL显示在孵育仅2分钟后就有统计学显著的抑制作用，在4分钟和8分钟后类似。对过氧亚硝酸盐自由基的影响与之前测试中观察到的一致。高浓度和短孵育时间表明对PMN活力没有干扰，因此抑制结果必须归因于药物的作用。DC的抗炎作用不能仅仅归因于对前列腺素合成的抑制，但其对自由基和中性粒细胞爆发的影响表明它们可能有助于其最终的治疗效果。
