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白藜芦醇对三氯乙烯致斑马鱼胚胎心脏发育毒性的保护作用。

Protective effects of resveratrol against the cardiac developmental toxicity of trichloroethylene in zebrafish embryos.

机构信息

School of Public Health, Medical College of Soochow University, Suzhou, China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, China.

School of Biology and Basic Medical Sciences, Medical College of Soochow University, Suzhou, China.

出版信息

Toxicology. 2021 Mar 30;452:152697. doi: 10.1016/j.tox.2021.152697. Epub 2021 Jan 29.

Abstract

Trichloroethylene (TCE), a prevalent environmental contaminant, has been shown to induce cardiac malformations. Resveratrol (RSV) is a natural polyphenolic compound exhibiting protective effects on heart development. To investigate if RSV could protect against TCE-induced heart defects, we exposed zebrafish embryos to TCE (10 ppb) in the presence or absence of RSV (1 μg/mL). Our results showed that RSV significantly attenuated TCE-induced heart defects in zebrafish embryos. The TCE-induced ROS (reactive oxygen species) generation, 8-OHdG (8-hydroxy-2`-deoxyguanosine) formation and cell proliferation were significantly counteracted by RSV. Moreover, RSV attenuated the TCE-induced changes in mRNA expression or activity of genes involved in AHR and Nrf2 signal pathways. We further showed that RSV might inhibit TCE-enhanced cell proliferation by rescuing the downregulation of the p53/p21 axis. In conclusion, our data demonstrates that RSV protects against the cardiac developmental toxicity of TCE by inhibiting AHR activity, oxidative stress and cell proliferation.

摘要

三氯乙烯(TCE)是一种常见的环境污染物,已被证明可导致心脏畸形。白藜芦醇(RSV)是一种天然多酚化合物,对心脏发育具有保护作用。为了研究 RSV 是否可以预防 TCE 引起的心脏缺陷,我们将斑马鱼胚胎暴露于 TCE(10ppb)中,同时存在或不存在 RSV(1μg/mL)。我们的结果表明,RSV 可显著减轻斑马鱼胚胎中 TCE 引起的心脏缺陷。RSV 显著抵消了 TCE 引起的 ROS(活性氧)生成、8-OHdG(8-羟基-2`-脱氧鸟苷)形成和细胞增殖。此外,RSV 减弱了 TCE 诱导的参与 AHR 和 Nrf2 信号通路的基因的 mRNA 表达或活性的变化。我们进一步表明,RSV 可能通过挽救 p53/p21 轴的下调来抑制 TCE 增强的细胞增殖。总之,我们的数据表明 RSV 通过抑制 AHR 活性、氧化应激和细胞增殖来防止 TCE 引起的心脏发育毒性。

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