EFFECTS OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS ON THE LUMINOL AND LUCIGENIN AMPLIFIED CHEMILUMINESCENCE OF HUMAN NEUTROPHILS

A panel of non-steroidal anti-inflammatory drugs commonly used for the rapeutic purposes was assessed for their effects on the respiratory bu rst of isolated human polymorphonuclear neutrophils. Cells were stimul ated with opsonised yeast and the production of reactive oxygen specie s was measured by amplified chemiluminescence with luminol and lucigen in which are two luminogenic agents measuring different cellular event s. A special attention was devoted to the establishment of dose-effect curves and calculation of ED50. Some of the drugs tested (acemetacine , diclofenac, flufenamic acid and niflumic acid) were able to decrease both luminol and lucigenin chemiluminescence in a dose-dependent mann er reflecting an inhibitory effect on the respiratory burst. The most potent derivative was flufenamic acid (ED50 8 and 78 mu M, respectivel y, with luminol and lucigenin), followed by diclofenac (21 and 98 mu M ), niflumic acid (97 and 227 mu M) and acemetacine (585 and 427 mu M). In contrast, several other drugs (flurbiprofen, ibuprofen, ketoprofen , piroxicam) stimulated both luminol and lucigenin chemiluminescence, suggesting a pro-oxidant activity. Acetylsalicylic acid (up to 1250 mu M) was a modest inhibitor (maximum 25% inhibition) showing no dose-de pendant effect and tolmetin (up to 125 mu M) had no significant effect in both systems. The results were in agreement using both luminogenic agents, except for indomethacin, naproxen and tenoxicam which showed different kinds of effects. The unspecific and complex nature of the m easurement systems used did not allow to give a complete mechanistic i nterpretation of the results, but the comparison with literature data gave some pertinent explanations for both anti- and pro-oxidant effect s. (C) 1998 Elsevier Science B.V. All rights reserved.