Enhanced antioxidant activity after chlorination of quercetin by hypochlorous acid

Background: Several epidemiological studies indicate that moderate consumpt ion of red wine decreases both the: incidence and mortality associated with cardiovascular disease. Quercetin and rutin (quercetin-3-rutinoside) are p olyphenols present in relatively large concentrations in red wine and may p lay a role in this cardioprotective phenomenon. The precise mechanisms of c ardioprotection remain unclear but may involve the action of these polyphen ols as antioxidants, which attenuate the tissue injury that results from th e production of proinflammatory oxidants such as hypochlorous acid (HOCl). Methods: To study the interaction of these polyphenols with proinflammatory oxidants, we mixed quercetin or rutin with HOCl (0-150 muM) and analyzed t he reaction products by high-performance liquid chromatography. mass spectr ometry, and nuclear magnetic resonance. Results: Stable mono- and dichlorinated derivates were detected for both qu ercetin and the glycoside derivative, rutin, which suggests that both the c onjugated and unconjugated forms of quercetin reacted with HOCl similarly. Chlorination of quercetin occurred only at two sites, and the derivates (6- chloroquercetin, 6,8-dichloroquercetin) were more potent antioxidants towar d oxidative modification of low-density lipoproteins and ABTS radical forma tion than the unmodified form. Conclusions: These data suggest that under certain pathological conditions in vivo (e.g., inflammation), flavonols may be converted to chlorinated der ivates, which er;exhibit an enhanced antioxidant potential and thereby play a role in cardioprotection.