Similar hepatotoxicity response induced by Rhizoma Paridis in zebrafish larvae, cell and rat.
Similar hepatotoxicity response induced by Rhizoma Paridis in zebrafish larvae, cell and rat.
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DOI：
10.1016/j.jep.2019.112440
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发表时间：
2019-11
影响因子：
5.4
通讯作者：
Chongjun Zhao;Mingshuang Wang;Zhe Jia;Erwen Li;Xia Zhao;Farong Li;Ruichao Lin
中科院分区：
文献类型：
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作者：
Chongjun Zhao;Mingshuang Wang;Zhe Jia;Erwen Li;Xia Zhao;Farong Li;Ruichao Lin
重楼作为一味中药，在临床使用已有数千年的历史。最近，一些发表的文章报道了其肝毒性，但其肝毒性机制尚未明确。因此，本研究旨在确定重楼治疗对脂质沉积和代谢、氧化应激和线粒体功能障碍的影响，并通过 L02 细胞、大鼠和斑马鱼幼虫探索潜在的分子机制。细胞培养中评估，与对照组相比，重楼可降低细胞活性和细胞增殖，导致细胞凋亡，并升高丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平。重楼可引起大鼠模型和斑马鱼幼虫肝脏结构和肝功能的改变。我们的结果表明，重楼可以增加肝脏脂质积累，这与之前的研究相似，可能是通过强化脂肪酸脂肪生成、抑制脂肪降解而发挥毒性作用。同时，本实验强调了氧化应激、线粒体功能障碍、内质网功能和炎症反应在重楼诱导的肝脏脂质代谢紊乱中的重要性，为解释重楼暴露引起脊椎动物脂质代谢紊乱提供了新的机制。此外，本实验结果表明，斑马鱼幼虫的毒性反应与常规模型相似，具有显着优势。
Rhizoma Paridis, as a Traditional Chinese Medicine (TCM), has been used in clinic for thousands of years. Recently, the hepatic toxicity was reported in some published articles while its hepatotoxicity mechanisms have not been well established. Therefore, the present study was performed to determine the effect of Rhizoma Paridis treatment on the lipid deposition and metabolism, oxidative stress and mitochondrial dysfunction, and explore the underlying molecular mechanism through L02 cell, rat and zebrafish larvae. Rhizoma Paridis could diminish cell activity and cell proliferation, brought on cell apoptosis and elevated the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with the control group, as evaluated in cell cultures. Rhizoma Paridis could result in the change of the liver structure and the liver function in the rat model and zebrafish larvae. Our results showed that Rhizoma Paridis could increase hepatic lipid accumulation, which was similar to the previous study and probably exerted toxic effect through intensive fatty acid lipogenesis, inhibition of fat degradation. Meanwhile, this experiment highlighted the importance of the oxidative stress, mitochondrial dysfunction, ER function, and the inflammation response in Rhizoma Paridis-induced disorder of hepatic lipid metabolism, which proposed a novel mechanism for interpretation of Rhizoma Paridis exposure inducing the disorder of lipid metabolism in vertebrates. Furthermore, the result of this experiment suggested that the toxicity response of zebrafish larvae was similar to the conventional model with a significant advantage.