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二烯丙基三硫醚,一种大蒜多硫化物,通过激活 Nrf2/ARE 信号通路,防止砷诱导的肾氧化应激毒性、细胞凋亡和炎症。

Diallyl trisulfide, a garlic polysulfide protects against As-induced renal oxidative nephrotoxicity, apoptosis and inflammation in rats by activating the Nrf2/ARE signaling pathway.

机构信息

Department of Zoology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India.

Department of Zoology, Faculty of Science, Annamalai University, Annamalainagar 608002, Tamilnadu, India.

出版信息

Int Immunopharmacol. 2017 Sep;50:107-120. doi: 10.1016/j.intimp.2017.06.011. Epub 2017 Jun 23.

DOI:10.1016/j.intimp.2017.06.011
PMID:28648972
Abstract

BACKGROUND

Arsenic (As) contamination is an extremely dangerous global environmental problem as it can enter into the food chain and become bio-accumulated, endangering human health. Chronic As intoxication leads to undesirable toxic effects in various organ systems of the body, especially the kidney. Diallyl trisulfide (DATS) is an organosulfur compound which has been widely known for its uses as antibacterial, antitumorogenic, antioxidant agent and has been also reported to have anti-apoptotic and anti-inflammatory properties.

PURPOSE

In the present work, we intend to investigate the protective role of DATS, a garlic organosulfur compound in preventing the As-induced oxidative stress mediated renal injury in rats. Study design The activity of DATS to antagonize As-induced renal oxidative toxicity was analyzed using rats as an in vivo model.

METHODS

We investigated the nephroprotective effect of DATS on As treated rats by performing various serological, biochemical, molecular and histological studies. The activation of Nrf2 was investigated using western blot.

RESULTS

The data showed that As exposure significantly increased the serum and urine nephritic, oxidative stress, apoptosis and inflammatory markers in the renal tissue of rats. As intoxication also decreased the antioxidant status of the renal tissue along with the disturbances in the membrane bound ATPases. As nephrotoxicity was further confirmed with the altered morphological and ultrastructural changes in the renal tissue. Conversely, the DATS pre-administration effectively recuperate the altered renal variables by As, which has been further supported by the histological and ultrastructural observations. This counteraction was achieved partially via the activation of Nrf2-ARE pathway through the activation of Akt.

CONCLUSION

These findings explicate the prospective use of DATS as a promising organosulfur compound against As-induced renal oxidative dysfunction in rats.

摘要

背景

砷(As)污染是一个极其危险的全球环境问题,因为它可以进入食物链并被生物累积,从而危害人类健康。慢性砷中毒会导致身体各器官系统产生不良的毒性作用,尤其是肾脏。二烯丙基三硫醚(DATS)是一种有机硫化合物,因其具有抗菌、抗肿瘤、抗氧化作用而被广泛应用,并且还具有抗凋亡和抗炎作用。

目的

本研究旨在探讨大蒜有机硫化合物 DATS 对预防大鼠砷诱导的氧化应激介导的肾损伤的保护作用。

研究设计

采用大鼠作为体内模型,分析 DATS 拮抗砷诱导肾氧化毒性的活性。

方法

通过进行各种血清学、生化、分子和组织学研究,研究 DATS 对砷处理大鼠的肾保护作用。采用 Western blot 检测 Nrf2 的激活情况。

结果

数据显示,砷暴露显著增加了大鼠血清和尿液中的肾毒性、氧化应激、凋亡和炎症标志物,以及肾组织中的抗氧化状态,同时还扰乱了膜结合 ATP 酶。砷肾毒性还伴随着肾组织形态和超微结构的改变。相反,DATS 预处理通过激活 Akt 部分通过 Nrf2-ARE 通路有效地恢复了砷改变的肾变量。

结论

这些发现阐明了 DATS 作为一种有前途的有机硫化合物,可用于预防大鼠砷诱导的肾氧化功能障碍。

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