Quercetin reduces oxidative damage induced by paraquat via modulating expression of antioxidant genes in A549 cells

Oxidative injury can occur in the lung through the generation of reactive oxygen species (ROS) via redox cycling owing to intentional or accidental ingestion of paraquat (PQ), a common herbicide. A wide array of phytochemicals has been shown to reduce cellular oxidative damage by modulating cytoprotective genes. Quercetin, a well-known flavonoid, has been reported to display cytoprotective effects by up-regulating certain cytoprotective genes. In this context, we investigated the effect of quercetin on PQ-induced cytotoxicity in alveolar A549 cells, modulation of antioxidant genes, activation of transcription factor-Nrf2 and its target HO-1 expression. Quercetin reduced PQ-induced cytotoxicity in A549 cells that was evaluated by both 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Modulation of antioxidant genes was compared when cells were treated with PQ, quercetin and both using qRT-PCR. Activation of transcription factor-Nrf2 and induction of its target gene, HO-1 was demonstrated by western blot analysis. A remarkable reduction in the ROS level as well as an increase in the total cellular glutathione (GSH) level occurred when PQ-exposed cells were treated with quercetin. Our findings suggest that quercetin may be used to mitigate or minimize oxidative stress via reducing the generation of ROS. Copyright (c) 2012 John Wiley & Sons, Ltd.