Dinis-Oliveira R J, Duarte J A, Sánchez-Navarro A, Remião F, Bastos M L, Carvalho F
REQUIMTE, Departamento de Toxicologia, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
Crit Rev Toxicol. 2008;38(1):13-71. doi: 10.1080/10408440701669959.
Paraquat dichloride (methyl viologen; PQ) is an effective and widely used herbicide that has a proven safety record when appropriately applied to eliminate weeds. However, over the last decades, there have been numerous fatalities, mainly caused by accidental or voluntary ingestion. PQ poisoning is an extremely frustrating condition to manage clinically, due to the elevated morbidity and mortality observed so far and due to the lack of effective treatments to be used in humans. PQ mainly accumulates in the lung (pulmonary concentrations can be 6 to 10 times higher than those in the plasma), where it is retained even when blood levels start to decrease. The pulmonary effects can be explained by the participation of the polyamine transport system abundantly expressed in the membrane of alveolar cells type I, II, and Clara cells. Further downstream at the toxicodynamic level, the main molecular mechanism of PQ toxicity is based on redox cycling and intracellular oxidative stress generation. With this review we aimed to collect and describe the most pertinent and significant findings published in established scientific publications since the discovery of PQ, focusing on the most recent developments related to PQ lung toxicity and their relevance to the treatment of human poisonings. Considerable space is also dedicated to techniques for prognosis prediction, since these could allow development of rigorous clinical protocols that may produce comparable data for the evaluation of proposed therapies.
百草枯二氯化物（甲基紫精；PQ）是一种有效且广泛使用的除草剂，在适当使用以消除杂草时具有可靠的安全记录。然而，在过去几十年中，发生了许多死亡事件，主要是由意外或自愿摄入引起的。由于迄今为止观察到的发病率和死亡率升高，以及缺乏用于人类的有效治疗方法，PQ中毒在临床上是一种极其棘手的病症。PQ主要积聚在肺部（肺部浓度可比血浆中的浓度高6至10倍），即使血液水平开始下降，它仍会在肺部留存。肺部效应可以通过在I型、II型肺泡细胞和克拉拉细胞的膜中大量表达的多胺转运系统的参与来解释。在毒理学水平的更下游，PQ毒性的主要分子机制基于氧化还原循环和细胞内氧化应激的产生。通过本综述，我们旨在收集和描述自PQ发现以来在权威科学出版物中发表的最相关和重要的发现，重点关注与PQ肺毒性相关的最新进展及其与人类中毒治疗的相关性。相当多的篇幅也致力于预后预测技术，因为这些技术可以允许制定严格的临床方案，这些方案可能产生可比的数据用于评估所提出的治疗方法。
