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葛根素通过抑制细胞凋亡和恢复自噬流来防止镉诱导的肝细胞损伤。

Puerarin prevents cadmium-induced hepatic cell damage by suppressing apoptosis and restoring autophagic flux.

机构信息

Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, PR China; Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611130, PR China.

Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, PR China; Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611130, PR China.

出版信息

Biomed Pharmacother. 2019 Jul;115:108929. doi: 10.1016/j.biopha.2019.108929. Epub 2019 May 3.

DOI:10.1016/j.biopha.2019.108929
PMID:31060001
Abstract

Cadmium (Cd) is a common heavy metal contamination that is highly toxic to liver. Puerarin (PU), a potent free radical scavenger, has been shown to exert cytoprotective effect in numerous pathological processes. However, whether PU affords protection against Cd-induced hepatotoxicity remains unclear to be known. Here, we aimed to investigate the protective effect of PU on Cd-induced hepatotoxicity in an immortalized mouse hepatocyte line, AML-12. First, Cd-induced cytotoxicity in AML-12 cells was obviously ameliorated by PU treatment. Also, Cd-induced apoptotic cell death was markedly alleviated by PU treatment, evidenced by two methods. Simultaneously, Cd-elevated malondialdehyde and reactive oxygen species levels were significantly reduced by PU administration, demonstrating the antioxidant effect of PU against Cd exposure. Moreover, Cd-induced blockage of autophagic flux in AML-12 cells was obviously restored by PU treatment, evidenced by immunoblot analysis of autophagy marker proteins and tandem fluorescent-tagged LC3 method. Resultantly, Cd-induced autophagosome accumulation was significantly alleviated by PU treatment. In conclusion, these observations demonstrate that PU treatment alleviates Cd-induced hepatic cell damage by inhibiting apoptosis and restoring autophagy activity, which is intimately related with its antioxidant activity.

摘要

镉 (Cd) 是一种常见的重金属污染,对肝脏有剧毒。葛根素 (PU) 是一种强效的自由基清除剂,已被证明在许多病理过程中具有细胞保护作用。然而,葛根素是否能对抗 Cd 诱导的肝毒性尚不清楚。在这里,我们旨在研究葛根素对 AML-12 永生化小鼠肝细胞系中 Cd 诱导的肝毒性的保护作用。首先,葛根素处理明显改善了 Cd 诱导的 AML-12 细胞的细胞毒性。此外,葛根素处理明显减轻了 Cd 诱导的细胞凋亡死亡,这两种方法都有证据表明。同时,葛根素给药显著降低了 Cd 引起的丙二醛和活性氧水平,表明葛根素具有抗氧化作用,能抵抗 Cd 暴露。此外,Cd 诱导的 AML-12 细胞自噬流阻断明显被葛根素处理所恢复,这一点通过自噬标志物蛋白的免疫印迹分析和串联荧光标记 LC3 方法得到证明。结果,葛根素处理明显减轻了 Cd 诱导的自噬体积累。总之,这些观察结果表明,葛根素处理通过抑制细胞凋亡和恢复自噬活性来减轻 Cd 诱导的肝损伤,这与其抗氧化活性密切相关。

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