Kładna Aleksandra, Aboul-Enein Hassan Y, Kruk Irena, Lichszteld Krzysztof, Michalska Teresa
Department of Medical History and Ethics, Pomeranian Medical Academy, Szczecin, Poland.
Biopolymers. 2006 Jun 5;82(2):99-105. doi: 10.1002/bip.20402.
Ketoprofen and tolmetin are widely used nonsteroidal anti-inflammatory drugs, whereas fenofibrate belongs to a family of hypolipidemic drugs used in the prevention of cardiovascular diseases. The aim of this study was to assess effect of these drugs on reactions generating reactive oxygen species (ROS). The following generators of ROS were used: 18-crown-6/KO(2) dissolved in DMSO as a source of superoxide radical (O(.-)(2), the Fenton-like reaction (Cu/H(2)O(2)) for hydroxyl radical (HO(.)), 2,2'-azobis (2-amidino-propane) dichloride (AAPH) as peroxyl radical (ROO(.)) generator, and a mixture of alkaline aqueous H(2)O(2) and acetonitrile for singlet oxygen ((1)O(2)). Measurements were done using chemiluminescence, fluorescence, and spin-trapping with 2,2,6,6-tetramethylpiperidine combined with electron spin resonance spectroscopy (ESR), and a deoxyribose assay based on the spectrophotometry. The results obtained demonstrated that all tested drugs were active against O(.-)(2). There was a clear ranking of drug inhibition effects on chemiluminescence from the O(.-)(2) system: ketoprofen > tolmetin > fenofibrate. The examined compounds inhibited the HO(.)-dependent deoxyribose degradation and scavenged the ROO(.) concentration dependently with an order of potencies similar to that of the superoxide radical system. Hence, these results indicate that the studied drugs show broad ROS scavenging property and, as a consequence, might decrease tissue damage due to the ROS and thus to contribute to anti-inflammatory therapy.
酮洛芬和托美丁是广泛使用的非甾体抗炎药,而非诺贝特属于用于预防心血管疾病的降血脂药物家族。本研究的目的是评估这些药物对产生活性氧(ROS)反应的影响。使用了以下ROS生成剂:溶解在二甲基亚砜中的18-冠-6/超氧化钾作为超氧阴离子自由基(O₂⁻)的来源,用于生成羟基自由基(·OH)的类芬顿反应(铜/过氧化氢),2,2'-偶氮双(2-脒基丙烷)二氯化物(AAPH)作为过氧自由基(ROO·)的生成剂,以及碱性过氧化氢水溶液和乙腈的混合物用于生成单线态氧(¹O₂)。测量采用化学发光、荧光、与2,2,6,6-四甲基哌啶结合的自旋捕获并结合电子自旋共振光谱(ESR),以及基于分光光度法的脱氧核糖测定法。获得的结果表明,所有测试药物对O₂⁻均有活性。从O₂⁻系统对化学发光的药物抑制作用有一个明显的排序:酮洛芬>托美丁>非诺贝特。所研究的化合物抑制依赖于·OH的脱氧核糖降解,并以与超氧阴离子自由基系统相似的效力顺序依赖性地清除ROO·浓度。因此,这些结果表明,所研究的药物具有广泛的ROS清除特性,因此可能会减少由于ROS导致的组织损伤,从而有助于抗炎治疗。