Protective effects of polydatin against sulfur mustard-induced hepatic injury
Protective effects of polydatin against sulfur mustard-induced hepatic injury
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虎杖甙对芥子气性肝损伤的保护作用
DOI：
10.1016/j.taap.2019.01.013
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发表时间：
2019
影响因子：
3.8
通讯作者：
Xiao Kai
中科院分区：
文献类型：
--
作者：
Zhang Hao;Chen Yongchun;Pei Zhipeng;Gao Huanhuan;Shi Wenwen;Sun Mingxue;Xu Qingqiang;Zhao Jie;Meng Wenqi;Xiao Kai
芥子气（SM）是一种化学战剂，在一系列军事冲突中使用，仍然对平民和军事人员构成严重威胁。虽然SM毒性的细胞和分子机制仍不完全清楚，但氧化应激已被认为是损伤的初始重要过程。白藜芦醇苷是白藜芦醇和葡萄糖的产物，是治疗氧化应激相关疾病的一种有前途的候选药物。然而，其对SM诱导的肝损伤的影响仍然未知。因此，我们研究了虎杖苷对SM诱导的肝损伤的保护作用及其可能的机制。结果表明，虎杖苷能显著提高SM皮下注射小鼠的存活率。虎杖苷可降低SM引起的血清转氨酶水平升高，减轻肝脏病理损伤。我们还发现，小鼠肝脏样品和L02细胞中的氧化应激指标得到改善。同时，在小鼠和细胞中探索了SM处理后Sirtuin家族的变化，因为虎杖苷是Sirt 1和Sirt 3的有效激活剂。虎杖苷显著增加小鼠肝脏和L02细胞中Sirt 1、HO-1和NQO 1的表达;以及Nrf 2的核转位。此外，我们还观察到，无论是Sirt 1或Nrf 2敲低取消了白藜芦醇苷的保护作用。我们的数据表明，白藜芦醇苷可以通过Sirt 1/Nrf 2途径提供对SM诱导的肝损伤的保护，这表明白藜芦醇苷是一种新的潜在的解毒剂硫芥子气。
Sulfur mustard (SM) is a chemical warfare agent that was applied in a series of military conflicts and still poses a severe threat to civilians and military personnel. Although the cellular and molecular mechanisms of SM toxicity are still not fully understood, oxidative stress has been considered as the initial vital process for damage. Polydatin, the product of resveratrol and glucose, is a promising candidate for the treatment of oxidative stress-related diseases. However, its effects on SM-induced hepatic injury remain unknown. Thus, we investigated the protective effects of polydatin against SM-induced hepatic injury and its possible mechanism. We found that treatment with polydatin remarkably improved the survival rate of mice bear subcutaneously injected with SM. Polydatin decreased the SM-induced increase of serum aminotransferase levels and ameliorated hepatic pathological damage. We also found that indexes of oxidative stress were improved in mouse liver samples and L02 cells. Meanwhile, changes in the Sirtuin family after treatment with SM were explored in mice and cells since polydatin is a potent activator of Sirt1 and Sirt3. Polydatin significantly increased the expression of Sirt1, HO-1, and NQO1; and the nuclear translocation of Nrf2 in mouse liver and L02 cells. Furthermore, we also observed that either Sirt1 or Nrf2 knockdown abolished the protective effect of polydatin. Our data indicated that polydatin could provide protection against SM-induced hepatic injury through the Sirt1/Nrf2 pathway, suggesting that polydatin is a novel potential antidote for sulfur mustard.