In vivo and in vitro evidence for the involvement of Nrf2-antioxidant response element signaling pathway in the inflammation and oxidative stress induced by particulate matter (PM10): the effective role of gallic acid.

Environmental pollution is one of the risk factors for respiratory diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is the major mechanisms contributing to cellular defense against oxidative damage. Gallic acid (GA) is regarded as potent anti-inflammatory and antioxidant agents. The aim was to evaluate the role of Nrf2 pathway in particulate matter (PM10) exposure on lung and epithelial cells with an emphasis on the role of GA. In in vivo part, the rats were divided as control, GA (30 mg/kg), particulate matter (PM) (0.5, 2.5, and 5 mg/kg), and PM + GA. In in vitro study, the cells were divided as control, PM10 (100, 250, and 500 µg/ml), GA (50 µmol/L) and PM10+GA. Inflammation, oxidative stress and Nrf2-pathway factors were assessed. PM10 groups showed a considerable increase in the epithelial permeability and inflammatory parameters. We also found a significant decrease in the expression of Nrf2 and its up-stream regulators genes. Accordingly, the biosynthesis of glutathione (GSH) and other antioxidant activities significantly decreased. Gallic acid was identified to restore the antioxidant status to the normal levels. Our findings approved that Nrf2 is involved in PM10-induced oxidative damages and showed that Nrf2 activation by natural agents could ameliorate respiratory injuries induced by PM10.