Abstract
Oxidative injury can occur in the lung through the generation of reactive oxygen species (ROS) via redox cycling due 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 cellular cytotoxicity in alveolar A549 cells, modulation of antioxidant genes, activation of transcription factor-Nrf2 and HO-1 (a gene target of Nrf-2). After 24 h of treatment, quercetin reduced PQ-induced cytotoxicity in A549 cells that was evaluated by both MTT and LDH assays. Modulation of antioxidant genes was compared when cells were treated with PQ, quercetin and both paraquat and quercetin by 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 ROS as well as increases in cellular GSH 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 reactive oxygen species but need further evaluation.
