Antiradical and chelating effects in flavonoid protection against silica-induced cell injury.

Quercetin, dihydroquercetin, and rutin are capable of scavenging superoxide anion (rate constants of the reaction with superoxide at pH 10 were 1.7 x 10(5), 1.5 x 10(5), and 0.5 x 10(5) M-1 s-1, respectively). At the same time rutin and quercetin but not dihydroquercetin are iron ion chelators. These substances were used to elucidate the role of radical scavenging and iron chelating in flavonoid protection against asbestos-induced oxidative cellular injury. Exposure of rat peritoneal macrophages to chrysotile asbestos fibers resulted in "frustrated" phagocytosis, cell injury, and a LDH release. Quercetin, dihydroquercetin, and rutin were effective in protecting the phagocytic cells against injury caused by asbestos. Moreover, these flavonoids exhibited cellular protection in the same order of effectiveness as that observed for the quenching of superoxide: quercetin > dihydroquercetin > rutin. Exposure of human red blood cells to asbestos fibers also caused progressive cell injury and lysis. Quercetin and rutin protected the red cells (quercetin > rutin), whereas dihydroquercetin was ineffective in preventing asbestos-induced hemolysis. The protective ability of quercetin and rutin may be related to their iron-chelating activity. Due to this these flavonoids can be located on asbestos surface in sites of initiation of free radical reactions and their antiradical moieties can scavenge reactive oxygen species immediately after the appearance. Thus, both antiradical and chelating effects appear to be involved in the flavonoid protection against silica-induced cell injury. Copyright 1998 Academic Press.