College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
Ecotoxicol Environ Saf. 2020 Mar 1;190:110064. doi: 10.1016/j.ecoenv.2019.110064. Epub 2019 Dec 26.
Astilbin (ASB), a dihydroflavonol glycoside, is widely found in a variety of plants and in functional foods and acts as a powerful antioxidant. The aim of this study was to investigate the underlying mechanisms involved in the antagonistic effects of ASB on cadmium (Cd)-induced necroptosis in chicken peripheral blood lymphocytes. Peripheral blood lymphocytes were aseptically collected from Roman white hens and then randomly divided into five groups: the control group was incubated without additional reagents, while the other groups were incubated with Cd, ASB, a combination of Cd and ASB, and 0.1% DMSO. After a 24 h treatment, cell samples were collected. The results showed that some morphological changes consistent with necroptosis were observed in the Cd-treated groups, suggesting the occurrence of necroptosis. Simultaneously, antioxidant activity markers (CAT, SOD, GSH, GSH-px, and T-AOC) decreased and indicators of oxidative stress (MDA, iNOS, NO, HO, ·OH and ROS) increased. The production of ROS induced the activation of the PI3K/Akt signaling pathway, as the expression levels of PI3K, Akt and PDK1 were significantly elevated. Additionally, the expression levels of RIPK3, RIPK1, MLKL, TAK1, TAB2 and TAB3 were increased and that of Caspase-8 was decreased, which could cause the necroptosis. However, the most important our results was that ASB supplements remarkably attenuated the Cd-induced effects. We conclude that the Cd treatment promoted an imbalance of the antioxidant status and activated the PI3K/Akt pathway, leading to necroptosis in chicken peripheral blood lymphocytes, and that ASB was able to partially ameliorate the effect of Cd-induced necroptosis.
梓醇（ASB）是一种二氢黄酮醇糖苷，广泛存在于多种植物和功能性食品中，具有强大的抗氧化作用。本研究旨在探讨 ASB 拮抗镉（Cd）诱导鸡外周血淋巴细胞坏死性凋亡的作用机制。无菌采集罗曼白母鸡外周血淋巴细胞，随机分为 5 组：对照组不添加额外试剂，其余各组分别用 Cd、ASB、Cd 和 ASB 混合物、0.1%DMSO 孵育 24h 后收集细胞样本。结果表明，Cd 处理组出现了一些与坏死性凋亡一致的形态学变化，提示发生了坏死性凋亡。同时，抗氧化活性标志物（CAT、SOD、GSH、GSH-px、T-AOC）降低，氧化应激指标（MDA、iNOS、NO、HO、·OH 和 ROS）升高。ROS 的产生激活了 PI3K/Akt 信号通路，PI3K、Akt 和 PDK1 的表达水平显著升高。此外，RIPK3、RIPK1、MLKL、TAK1、TAB2 和 TAB3 的表达水平升高，Caspase-8 的表达水平降低，导致坏死性凋亡。然而，最重要的是，ASB 补充剂显著减轻了 Cd 诱导的作用。我们得出结论，Cd 处理促进了抗氧化状态的失衡，并激活了 PI3K/Akt 通路，导致鸡外周血淋巴细胞发生坏死性凋亡，而 ASB 能够部分改善 Cd 诱导的坏死性凋亡。
