Department of Anesthesiology, Faculty of Allied Medical Sciences, Kerman University of Medical Sciences, Kerman, Iran; Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Department of Toxicology and Pharmacology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
Toxicology. 2020 Mar 30;433-434:152407. doi: 10.1016/j.tox.2020.152407. Epub 2020 Feb 12.
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.
百草枯（PQ）是一种快速有效的除草剂，在全世界范围内用于除草。在过去的几年中，PQ 被认为是最受欢迎的自杀毒物之一，PQ 中毒约占全世界自杀人数的三分之一。PQ 中毒可导致多器官衰竭、肺纤维化，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。到目前为止，还没有找到治疗 PQ 中毒的有效解毒剂。一般来说，PQ 的毒性是由于形成高能氧自由基和细胞内不饱和脂质的过氧化作用。铁死亡是由于谷胱甘肽过氧化物酶 4（GPX4）活性丧失导致铁依赖性脂质过氧化物转化为在生物环境中惰性的脂质醇的结果。铁代谢和脂质过氧化的损伤越来越被认为是铁死亡的驱动因素。铁死亡在 PQ 中毒导致细胞死亡的发展中的作用尚未得到解决。越来越多的证据表明 PQ 中毒与铁死亡之间存在关联。这就提出了使用铁死亡抑制剂治疗 PQ 中毒的可能性。在这篇以假设为导向的综述文章中，我们详细阐述了铁死亡抑制剂如何规避 PQ 诱导的毒性，并且可能对 PQ 毒性的治疗具有潜在的用途。
