TY - JOUR PY - 2019// TI - Protective effects of polydatin against sulfur mustard-induced hepatic injury JO - Toxicology and applied pharmacology A1 - Zhang, Hao A1 - Chen, Yongchun A1 - Pei, Zhipeng A1 - Gao, Huanhuan A1 - Shi, Wenwen A1 - Sun, Mingxue A1 - Xu, Qingqiang A1 - Zhao, Jie A1 - Meng, Wenqi A1 - Xiao, Kai SP - 1 EP - 11 VL - 367 IS - N2 - 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.

Copyright © 2019. Published by Elsevier Inc.

Language: en

LA - en SN - 0041-008X UR - http://dx.doi.org/10.1016/j.taap.2019.01.013 ID - ref1 ER -