Apoptosis of lymphocytes is associated with immunosuppression and poor\nprognosis in sepsis. Our previous report showed that histones, nuclear proteins\nreleased from damaged or dying cells in sepsis, can mediate lymphocyte apoptosis\nvia mitochondria damage. Grape seed proanthocyanidin extract (GSPE), a natural\nsubstance with protective properties against oxidative stress, plays a vital role in\ncell and mitochondria protection. We thus hypothesized that GSPE may play a\nprotective role in histone-induced lymphocyte apoptosis through its anti-oxidative\nproperties. In this study, we investigated the protective efficacy of GSPE on\nlymphocyte apoptosis induced by extracellular histones, a main contributor of death\nin sepsis. Human blood lymphocytes were treated with 50 mg/ml histones, 2 mg/ml\nGSPE, or a combination of both. A total of 100 mM N-acetylcysteine (NAC), a\nreactive oxygen species (ROS) inhibitor, was used as a positive control for GSPE.\nApoptosis, intracellular ROS levels, mitochondrial membrane potential, Bcl-2\nexpression, and caspase-3 cleavage were measured. Our data clearly indicate that\nGSPE significantly inhibited lymphocyte apoptosis, generation of ROS, the loss of\nmitochondrial membrane potential, the decrease in Bcl-2 expression, and caspase-3\nactivation induced by extracellular histones. In conclusion, we show that GSPE\nhas a protective effect on lymphocyte apoptosis induced by extracellular histones.\nThis study suggests GSPE as a potential therapeutic agent that could help reduce\nlymphocyte apoptosis, and thus the state of immunosuppression was observed in\nseptic patients.
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