Scavenging of reactive oxygen species by some nonsteroidal anti-inflammatory drugs and fenofibrate.
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.
Kładna
Aleksandra
A
Department of Medical History and Ethics, Pomeranian Medical Academy, Szczecin, Poland.
Aboul-Enein
Hassan Y
HY
Kruk
Irena
I
Lichszteld
Krzysztof
K
Michalska
Teresa
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D011345:Fenofibrate / Q000494:pharmacology*; D005453:Fluorescence; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007660:Ketoprofen / Q000494:pharmacology; D008163:Luminescent Measurements; D010100:Oxygen / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013113:Spin Labels; D019097:Spin Trapping; D013481:Superoxides / Q000378:metabolism; D014046:Tolmetin / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D000960:Hypolipidemic Agents; D010545:Peroxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D013481:Superoxides; C049375:perhydroxyl radical; D017665:Hydroxyl Radical; D007660:Ketoprofen; D014046:Tolmetin; D010100:Oxygen; D011345:Fenofibrate