The amplified chemiluminescence test to characterize antirheumatic drugs as oxygen radical scavengers

High levels of reactive oxygen species (ROS) are generated by phagocytes involved in host defence and inflammation. Thus, it appears highly desirable to learn more about the potential of antirheumatic drugs to scavenge ROS or to inhibit their enzymatic generation. Amplified chemiluminescence (CL) allows detection of O-2 using lucigenin (LgCL) or H2O2 using luminol (LuCL). A total of 43 compounds have been tested quantitatively in vitro (10(-6) to 10(-4) mol/l) with respect to three test parameters; varying cell-activity, and incubation-time employing two different phagocyte populations (neutrophils/macrophages). The most active compounds with LgCL were the known radical scavengers nordihydroguaiaretic acid (NDGA), N-propyl gallate, superoxide dismutase and chloroquine, the non-steroidal anti-inflammatory drugs (NSAID) benzydamine, timegadine, carprofen, enolicam, the known lipoxygenase inhibitors (e.g. CBS 1108/1114, BW 755C) and glucosaminoglucan polysulfate. Inactive in this system were corticosteroids (prednisolone, dexamethasone) most of the tested NSAID (N = 16/20), most disease modifying drugs (D-penicillamine, levamisole, gold-TM) and the anti-gout drugs (sulfinpyrazone, allopurinol, colchicine). Therefore amplified CL with lucigenin appears to be a rapid, kinetic, reproducible means of pharmacological profiling in vitro new anti-inflammatory drugs for radical scavenger activity.