College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, People's Republic of China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, People's Republic of China; College of Veterinary Medicine, Northwest A & F University, Yangling 712100, People's Republic of China.
Toxicol In Vitro. 2017 Oct;44:349-356. doi: 10.1016/j.tiv.2017.07.027. Epub 2017 Jul 29.
Cadmium (Cd) is a ubiquitously distributed trace metal and environmental pollutant that is highly toxic to liver. Selenium (Se) may provide chemoprotection against Cd-induced cytotoxicity by augmenting the cellular antioxidant capacity. However, the mechanism of Se chemoprotection against Cd-induced hepatotoxicity is unclear. The present study evaluated the ameliorative properties of Se against Cd-induced cytotoxicity in hepatocytes. Primary cells were exposed to 5μM Cd and/or 1μM Se for 24h. Cellular morphology and function, antioxidant status, activation of Nrf2 pathway, autophagy and apoptosis were determined. These results indicated that Se ameliorated the cytotoxicity of Cd by recovering hepatocyte morphology and function, inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) production, reducing intracellular LDH release, autophagy and apoptosis, and increasing the major antioxidative activities (Total antioxidant capacity (T-AOC) and superoxide dismutase (SOD). In summary, Cd is a hepatotoxin that causes hepatocytes damage by inducing oxidative stress, excessive autophagy and apoptosis as a mechanism of toxicity. Moreover, Se supplement ameliorated these effects by enhancing antioxidant systems, decreasing excessive autophagy and apoptosis. These results suggested that Se triggers Nrf2-mediated protection as the mechanism of Se chemoprotection against Cd-induced autophagy and apoptosis.
镉 (Cd) 是一种广泛分布的痕量金属和环境污染物，对肝脏具有高度毒性。硒 (Se) 可以通过增强细胞抗氧化能力提供对 Cd 诱导的细胞毒性的化学保护。然而，Se 对 Cd 诱导的肝毒性的化学保护机制尚不清楚。本研究评估了 Se 对肝细胞中 Cd 诱导的细胞毒性的改善作用。原代细胞暴露于 5μM Cd 和/或 1μM Se 24 小时。测定细胞形态和功能、抗氧化状态、Nrf2 通路的激活、自噬和细胞凋亡。这些结果表明，Se 通过恢复肝细胞形态和功能、抑制活性氧 (ROS) 和丙二醛 (MDA) 的产生、减少细胞内 LDH 释放、自噬和细胞凋亡、增加主要抗氧化活性 (总抗氧化能力 (T-AOC) 和超氧化物歧化酶 (SOD) 来改善 Cd 的细胞毒性。总之，Cd 是一种肝毒素，通过诱导氧化应激、过度自噬和凋亡作为毒性机制引起肝细胞损伤。此外，Se 补充通过增强抗氧化系统、减少过度自噬和凋亡来改善这些作用。这些结果表明，Se 通过触发 Nrf2 介导的保护作为 Se 对 Cd 诱导的自噬和凋亡的化学保护机制。
