Nrf2 protects against As(III)-induced damage in mouse liver and bladder.
Nrf2 protects against As(III)-induced damage in mouse liver and bladder.
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DOI：
10.1016/j.taap.2009.06.010
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发表时间：
2009-10-01
影响因子：
3.8
通讯作者：
Zhang DD
中科院分区：
文献类型：
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作者：
Jiang T;Huang Z;Chan JY;Zhang DD
砷化合物被归类为有毒物质和人类致癌物。环境暴露于砷在世界范围内造成了一个大的健康问题。砷通过许多机制发挥其毒性作用，包括产生活性氧（ROS）。Nrf 2是控制主要细胞抗氧化反应表达的主要转录因子，其是中和ROS并因此保护细胞免受外源性损伤所需的。在此之前，我们使用细胞培养模型证明了Nrf 2对砷诱导的毒性的保护作用。在本报告中，我们提供了证据，证明Nrf 2可以在小鼠模型中保护肝脏和膀胱免受六周砷暴露的损伤。与Nrf 2 +/+小鼠相比，Nrf 2 −/−小鼠在肝脏和膀胱中显示出更严重的病理变化。此外，Nrf 2 −/−小鼠对砷诱导的DNA低甲基化、氧化性DNA损伤和凋亡性细胞死亡更敏感。这些结果表明Nrf 2在体内对砷毒性具有保护作用。因此，这项工作证明了使用靶向激活Nrf 2信号通路的膳食化合物来减轻砷诱导的损伤的可行性。
Arsenic compounds are classified as toxicants and human carcinogens. Environmental exposure to arsenic imposes a big health issue worldwide. Arsenic elicits its toxic efforts through many mechanisms, including generation of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls expression of a main cellular antioxidant response, which is required for neutralizing ROS and thus defending cells from exogenous insults. Previously, we demonstrated a protective role of Nrf2 against arsenic-induced toxicity using a cell culture model. In this report, we present evidence that Nrf2 protects against liver and bladder injury in response to six-weeks of arsenic exposure in a mouse model. Nrf2−/− mice displayed more severe pathological changes in the liver and bladder, compared to Nrf2+/+ mice. Furthermore, Nrf2−/− mice were more sensitive to arsenic-induced DNA hypomethylation, oxidative DNA damage, and apoptotic cell death. These results indicate a protective role of Nrf2 against arsenic toxicity in vivo. Hence, this work demonstrates the feasibility of using dietary compounds that target activation of the Nrf2 signaling pathway to alleviate arsenic-induced damage.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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通讯作者：
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DOI：
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