PURPOSE: The objective of this study was to investigate the radioprotective effect of ferulic acid (FA) on irradiated lymphocytes and discover the possible mechanisms of protection. MATERIALS AND METHODS: Lymphocytes were pretreated for 12 h with FA (0.001-0.1 μM) and then exposed to 3 Gy radiation. Cell apoptosis, intracellular reactive oxygen species (ROS), and signal pathway was analysed. RESULTS: Irradiation increased cell death, DNA fragmentation and intracellular ROS. Pretreatment with FA significantly reversed this tendency and attenuated the irradiation-induced ROS generation. Furthermore, several anti-apoptotic characteristics of FA were determined, including the ability to diminish cytosolic Ca(2+) concentration, inhibit caspase-3 activation and cytochrome c translocation, upregulate B-cell lymphoma 2 (Bcl-2) and downregulate Bcl-2-associated X protein (Bax) in 3 Gy-irradiated lymphocytes. Signal pathway analysis showed FA decreased the activation of extracellular regulated kinase (ERK), which had been activated by radiation. CONCLUSION: The results suggest that FA had a radioprotective effect through the ERK pathway to inhibit apoptosis and oxidation, and it may be an effective candidate for treating radiation diseases associated with oxidative stress.
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