Lycopene Induces Expression of NAD(P)H Quinone Oxidoreductase and Heme Oxygenase-1 through Activation of Nrf2 in Ethanol/LPS-stimulated Pancreatic Acinar Cells

Abstract

ObjectivesHigh alcohol intake is a major risk factor for acute pancreatitis. Alcohol metabolism increases reactive oxygen species (ROS) and lipopolysaccharide (LPS) production, leading to induction of inflammatory cytokines such as IL-6 in pancreatic acinar (AR42J) cells. The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway is activated to induce the expression of antioxidant enzymes such as NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) as a cytoprotective response to oxidative stress. Lycopene, a bright-red carotenoid, is a potent antioxidant due to its high number of conjugated double bonds, which exerts anti-inflammatory and antioxidant effects. In this study, we investigated whether lycopene decreases ethanol/LPS-induced increase in ROS levels and IL-6 expression via Nrf2 signaling in AR42J cells.MethodsThe cells were pretreated with or without lycopene for 1 h, and treated with ethanol (250 mM) and LPS (10 mg/l) for 30 min (ROS levels, protein levels of NQO1, HO-1, pNrf2, Nrf2, and Keap1), 6 h (IL-6 mRNA expression), and 24 h (IL-6 protein level).ResultsLycopene increased the expression of NQO1 and HO-1 in ethanol/LPS-stimulated AR42J cells. The phosphorylation and nuclear translocation of Nrf2 were increased by lycopene in ethanol/LPS-stimulated AR42J cells. Lycopene decreased interaction between Keap1 and Nrf2 in AR42J cells, which may induce Nrf2 activation by inhibiting Keap1-mediated sequestration of Nrf2. Lycopene inhibited ethanol/LPS-induced increase in ROS levels and IL-6 expression in AR42J cells.ConclusionsIn conclusion, lycopene inhibits ROS-mediated IL-6 expression by promoting Nrf2-mediated expression of NQO1 and HO-1 in ethanol/LPS stimulated AR42J cells. Therefore, consumption of lycopene-rich foods may be beneficial for preventing the development of alcoholic acute pancreatitis by inhibiting oxidative stress and inflammatory cytokine production by activating Nrf2 signaling in pancreatic acinar cells.Funding SourcesThe Authors declare that there is no conflict of interest.