Paraquat (PQ) is a fast-acting and effective herbicide that is used throughout the world to eliminate weeds. Over the past years, PQ was considered one of the most popular poisoning substances for suicide, and PQ poisoning accounts for about one-third of suicides around the world. Poisoning with PQ may cause multiorgan failure, pulmonary fibrosis, and ultimately death. Exposure to PQ results in the accumulation of PQ in the lungs, causing severe damage and, eventually, fibrosis. Until now, no effective antidote has been found to treat poisoning with PQ. In general, the toxicity of PQ is due to the formation of high energy oxygen free radicals and the peroxidation of unsaturated lipids in the cell. Ferroptosis is the result of the loss of glutathione peroxidase 4 (GPX4) activity that transforms iron-dependent lipid hydroperoxides to lipid alcohols, which are inert in the biological environment. Impaired iron metabolism and lipid peroxidation are increasingly known as the driving agents of ferroptosis. The contribution of ferroptosis to the development of cell death during poisoning with PQ has not yet been addressed. There is growing evidence about the relationship between PQ poisoning and ferroptosis. This raises the possibility of using ferroptosis inhibitors for the treatment of PQ poisoning. In this hypothesis-driven review article, we elaborated how ferroptosis inhibitors might circumvent the toxicity induced by PQ and may be potentially useful for the treatment of PQ toxicity.

中文翻译：

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铁死亡抑制剂和百草枯解毒机制的交叉点，探索可能的治疗策略。

百草枯 (PQ) 是一种速效、有效的除草剂，在全世界范围内用于消除杂草。在过去的几年里，百草枯被认为是最常见的自杀中毒物质之一，百草枯中毒约占全球自杀事件的三分之一。PQ 中毒可能导致多器官衰竭、肺纤维化，并最终导致死亡。接触 PQ 会导致 PQ 在肺部积聚，造成严重损伤，最终导致纤维化。迄今为止，尚未找到治疗百草枯中毒的有效解毒剂。一般来说，PQ的毒性是由于细胞内高能氧自由基的形成和不饱和脂质的过氧化作用造成的。铁死亡是谷胱甘肽过氧化物酶 4 (GPX4) 活性丧失的结果，该酶将铁依赖性脂质氢过氧化物转化为在生物环境中呈惰性的脂质醇。铁代谢受损和脂质过氧化越来越被认为是铁死亡的驱动因素。铁死亡对 PQ 中毒期间细胞死亡发展的贡献尚未得到解决。越来越多的证据表明 PQ 中毒与铁死亡之间的关系。这提出了使用铁死亡抑制剂治疗 PQ 中毒的可能性。在这篇以假设为驱动的综述文章中，我们详细阐述了铁死亡抑制剂如何规避 PQ 引起的毒性，并可能对治疗 PQ 毒性有潜在作用。