Hydroxyl Radical-Scavenging Activity of Slow-Acting Anti-Rheumatic Drugs

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In this study, we verified the hydroxyl radical-scavenging activity (OH-SA) of slow-acting anti-rheumatic drugs (SARD's) and compared it with that of other ^.OH-scavengers such as dimethylsulfoxide (DMSO), glucose, albumin, and ethanol. For this purpose, we employed the electron spin resonance/spin trapping method in a cell-free system using two different concentrations of the spin trap 5′5′-dimethyl-1-pyrroline-N-oxide (DMPO). The use of two levels of DMPO concentrations made it possible to separate the true OH-SA of SARD's from the direct effects of SARD's on the Fe/H₂O₂ ^.OH-generating system, which can cause false values for OH-SA. The OH-SA was stronger in the following order: D-penicillamine (D-pen)>bucillamine>lobenzarit disodium (CCA)>DMSO>5-amino-salicylic acid (5-ASA)>albumin=acetyl-5-aminosalicylic acid>glucose>sulfasalazine (SASP)>ethanol. However, D-pen, CCA, 5-ASA, and albumin interfered with the Fe/H₂O₂ ^.OH-generating system. Auranofin and metabolites of SASP such as sulfapyridine and acetyl-sulfapyridine had no OH-SA in the cell-free system. None of the SARD's had a significant OH-SA at the concentrations reported in the plasma from patients taking these medications. Therefore, it is unlikely that SARD's act as true ^.OH-scavengers in the plasma. At sites of inflammation, however, SARD's may contribute to the scavenging of ^.OH produced as in the case of 5-ASA, since its concentration has been reported to be much higher in special sites such as the distal lumen of the bowel.