Quercetin Potentiates Toxicity Of Hemolytic Drugs In G6PD Deficient Human Erythrocytes

Abstract

Quercetin, a flavonoid, is widely distributed in plants and a prominent constituent of dietary supplements. Quercetin-based supplements are recommended for prevention of cancer, improvement of cardiovascular functions and mental health. However, these effects have not been validated clinically. Except for limited interactions with some drugs (fluoroquinolone antibiotics and taxol/paclitaxel), there is little evidence of safety concerns, and with oral use, quercetin-containing preparations have been generally well tolerated. Quercetin inhibits NRH: quinone oxidoreductase 2 (NQO2), an enzyme involved in quinone metabolism and detoxification. Individuals with genetic deficiency of glucose 6-phosphate dehydrogenase (G6PD) are highly susceptible to hemolytic toxicity of certain oxidant drugs. Treatment of G6PD deficient human erythrocytes in vitro with quercetin caused significant increase in methemoglobin formation and selective depletion of reduced glutathione (GSH) levels. Further, when tested in combination with 5, 6-orthoquinone PQ [6] and dapsone hydroxylamine [3], the hemotoxic metabolites of primaquine [4] and dapsone [2] respectively, caused significant potentiation of their hemotoxic effect as determined through an increase in methemoglobin formation and depletion of GSH. Quercetin also augmented the hemotoxic effect of 2-amino-4-chlorophenol in vitro. The results warrant further investigation of quercetin regarding its toxic interaction with drugs clinically known to cause hemolytic toxicity.