2021 · Scientific Reports · 程子译

Anthrahydroquinone-2-6-disulfonate is a novel, powerful antidote for paraquat poisoning

作者
Jin Qian; Chun-Yuan Wu; Dong-Ming Wu; Li-Hua Li; Qi Li; Tang Deng; Qi-Feng Huang; Shuang-Qin Xu; Hang-Fei Wang; Xin-Xin Wu; Zi-Yi Cheng; Chuan-Zhu Lv; Xiao-Ran Liu
期刊
Scientific Reports
DOI
10.1038/s41598-021-99591-4

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摘要

English abstract

Paraquat (PQ) is a widely used fast-acting pyridine herbicide. Accidental ingestion or self-administration via various routes can cause severe organ damage. Currently, no effective antidote is available commercially, and the mortality rate of poisoned patients is exceptionally high. Here, the efficacy of anthrahydroquinone-2-6-disulfonate (AH2QDS) was observed in treating PQ poisoning by constructing in vivo and ex vivo models. We then explored the detoxification mechanism of AH2QDS. We demonstrated that, in a rat model, the PQ concentration in the PQ + AH2QDS group significantly decreased compared to the PQ only group. Additionally, AH2QDS protected the mitochondria of rats and A549 cells and decreased oxidative stress damage, thus improving animal survival and cell viability. Finally, the differentially expressed genes were analysed in the PQ + AH2QDS group and the PQ group by NextGen sequencing, and we verified that Nrf2’s expression in the PQ + AH2QDS group was significantly higher than that in the PQ group. Our work identified that AH2QDS can detoxify PQ by reducing PQ uptake and protecting mitochondria while enhancing the body's antioxidant activity.

中文摘要

百草枯 (PQ) 是一种广泛使用的速效吡啶除草剂。意外摄入或通过各种途径自行给药可能会导致严重的器官损伤。目前,市场上尚无有效的解毒剂,中毒患者的死亡率极高。本研究通过构建体内和离体模型,观察蒽氢醌-2-6-二磺酸盐(AH2QDS)治疗百草枯中毒的疗效。然后我们探讨了AH2QDS的解毒机制。我们证明,在大鼠模型中,与仅使用 PQ 的组相比,PQ + AH2QDS 组的 PQ 浓度显着降低。此外,AH2QDS 保护大鼠和 A549 细胞的线粒体,减少氧化应激损伤,从而提高动物存活率和细胞活力。最后通过NextGen测序对PQ + AH2QDS组和PQ组的差异表达基因进行分析,验证PQ + AH2QDS组中Nrf2的表达量显着高于PQ组。我们的工作发现,AH2QDS 可以通过减少 PQ 摄取和保护线粒体来解毒 PQ,同时增强身体的抗氧化活性。

TOC / Graphical abstract

TOC / Graphical abstract
TOC / Graphical abstract