Oxidative stress in rheumatoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators.

The enhanced production of superoxide ion and peroxynitrite by bloodstream neutrophils and of superoxide ion by monocytes from rheumatoid arthritis (RA) patients was registered. It was suggested that NADPH oxidase together with NO synthase were the major sources of superoxide ion in RA neutrophils, while in RA monocytes superoxide ion was produced by NADPH oxidase and mitochondria. Among the different free radical inhibitors studied (antioxidant enzymes, SOD and catalase; free radical scavengers, bioflavonoid rutin and mannitol; and the iron chelator desferrioxamine), SOD and rutin were the most efficient suppressors of oxygen radical overproduction by RA neutrophils, while mannitol and desferrioxamine were inactive. Thus, in contrast to Fanconi anemia (FA) leukocytes (Korkina LG et al., J Leukocyte Biol 1992;52:357-62), iron-catalyzed hydroxyl radical formation was unimportant in RA leukocytes, which mainly produced superoxide ion. Natural non-toxic bioflavonoid rutin (vitamin P) inhibited oxygen radical overproduction in both RA and FA in an equally efficient manner and therefore may be considered as a useful supporting pharmaceutical agent for the treatment of "free radical" pathologies.