Lycopene alleviates H2O2-induced oxidative stress, inflammation and apoptosis in bovine mammary epithelial cells via the NFE2L2 signaling pathway

Abstract

During the transition into lactation, bovine mammary epithelial cells (bMECs) are likely subjected to altered redox balance due to the high metabolic rate associated with the onset of lactation. In non-ruminants, lycopene (LYC), a naturally occurring hydrocarbon carotenoid, has attracted considerable attention as a potential natural agent against oxidative stress. The aim of this study was to investigate whether LYC alleviates oxidative injury in bMECs induced by H₂O₂ and the underlying molecular mechanisms. The primary bMEC and bovine MEC line MAC-T cells were treated with H₂O₂ (500 μM) and/or LYC (0.5, 1 or 2 μM) for 24 h. The results showed that treatment with LYC decreased H₂O₂-induced accumulation of intracellular reactive oxygen species (ROS), inflammatory cytokine (TNF-α, IL-6, and IL-1β) expression and the apoptosis rate. These effects were associated with the activation of the NFE2L2-antioxidant response element (ARE) pathway coupled with inactivation of the nuclear factor-κB (NF-κB) inflammatory and caspase/Bcl2 apoptotic pathways. The bMECs were transfected with NFE2L2 siRNA for 48 h and/or treated with H₂O₂ (500 μM) and/or LYC (2 μM) for another 24 h. The fact that transfection with NFE2L2 siRNA abrogated the protection of LYC against H₂O₂-induced accumulation of intracellular ROS, inflammatory cytokine expression and apoptosis suggested that this antioxidant transcription factor is essential for the protective mechanism induced by LYC. These results suggest that LYC might be a potent antioxidant in vivo that could be administered to ruminant animals during stressful periods such as the transition into lactation.