College of Animal Science and Technology, Henan University of Science and Technology, No.263, Kaiyuan Avenue, 471023, Luoyang, PR China.
College of Animal Science and Technology, Henan University of Science and Technology, No.263, Kaiyuan Avenue, 471023, Luoyang, PR China.
Ecotoxicol Environ Saf. 2022 Aug;241:113772. doi: 10.1016/j.ecoenv.2022.113772. Epub 2022 Jun 14.
Cadmium (Cd) is one of the most toxic environmental pollutants. Quercetin (Que) is a kind of natural flavonoid with neuroprotective, antioxidant, and free-radical scavenging pharmacological activities. However, whether Que has the protective effect of on Cd-induced rat hepatocyte injury is unclear. This study aimed to determine the protective effect of Que on Cd-induced hepatotoxicity in vivo and in vitro. For in vivo, 36 4-week-old male SD rats were randomly divided into six groups and were treated with CdCl (2 mg/kg b.w.) and/or Que (50 or 100 mg/kg b.w.). Four weeks later, the rats were sacrificed and livers were collected. The levels of alanine aminotransferase, aspartate aminotransferase, glutathione, malondialdehyde, catalase, and superoxide dismutase were measured. Liver histopathological sections were made, and TUNEL method was performed to detect cell apoptosis. The mRNA and protein expression levels of endoplasmic reticulum stress (ERS) signaling pathway-related factors and apoptosis-related factors were detected. For in vitro, BRL-3A rat cells were treated with CdCl (12.5 μM) and/or Que (5 μM Que). The mRNA and protein expression levels of ERS signaling pathway-related factors and apoptosis-related factors were detected. Results showed that Cd led to liver injury, disorder of hepatocyte morphology and structure, decreased BRL-3A cells viabilities, increased oxidative damage. The mRNA and protein expression levels of ERS related factors GRP78, PERK, eIF2α, ATF4, CHOP, IRE1α, XBP1, and ATF6 increased. The mRNA and protein levels of apoptosis related factors Caspase12, Caspase3, and Bax increased, whereas Bcl2 decreased. It indicated that cadmium could activate PERK-eIF2α-ATF4-CHOP, IRE1α-XBP1, and ATF6-CHOP ERS-related signal pathways and lead to apoptosis. Moreover, Que can improve the vitality of hepatocytes, and effectively reduce hepatocytes damage, and reduce oxidative damage by Cd. As a result, the mRNA and protein expression levels of ERS related factors were reduced and hepatocyte apoptosis related factors decreased. Therefore, Que can be used as an effective component in daily diet to prevent Cd toxicity.
镉 (Cd) 是最具毒性的环境污染物之一。槲皮素 (Que) 是一种天然类黄酮，具有神经保护、抗氧化和自由基清除的药理活性。然而，槲皮素是否对镉诱导的大鼠肝细胞损伤具有保护作用尚不清楚。本研究旨在确定槲皮素对体内和体外镉诱导的肝毒性的保护作用。在体内，将 36 只 4 周龄雄性 SD 大鼠随机分为六组，分别用 CdCl（2mg/kg b.w.）和/或槲皮素（50 或 100mg/kg b.w.）处理。四周后，处死大鼠并收集肝脏。测定丙氨酸转氨酶、天冬氨酸转氨酶、谷胱甘肽、丙二醛、过氧化氢酶和超氧化物歧化酶的水平。制作肝组织病理切片，采用 TUNEL 法检测细胞凋亡。检测内质网应激（ERS）信号通路相关因子和凋亡相关因子的 mRNA 和蛋白表达水平。在体外，用 CdCl（12.5μM）和/或槲皮素（5μM 槲皮素）处理 BRL-3A 大鼠细胞。检测 ERS 信号通路相关因子和凋亡相关因子的 mRNA 和蛋白表达水平。结果表明，Cd 导致肝损伤，肝细胞形态和结构紊乱，BRL-3A 细胞活力下降，氧化损伤增加。ERS 相关因子 GRP78、PERK、eIF2α、ATF4、CHOP、IRE1α、XBP1 和 ATF6 的 mRNA 和蛋白表达水平增加。凋亡相关因子 Caspase12、Caspase3 和 Bax 的 mRNA 和蛋白水平升高，而 Bcl2 降低。这表明镉可以激活 PERK-eIF2α-ATF4-CHOP、IRE1α-XBP1 和 ATF6-CHOP ERS 相关信号通路并导致细胞凋亡。此外，槲皮素可以提高肝细胞活力，有效减轻镉引起的肝细胞损伤，降低氧化损伤。结果，ERS 相关因子的 mRNA 和蛋白表达水平降低，肝细胞凋亡相关因子减少。因此，槲皮素可以作为日常饮食中的有效成分，预防镉毒性。
