Department of Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
Br J Clin Pharmacol. 2011 Nov;72(5):745-57. doi: 10.1111/j.1365-2125.2011.04026.x.
Poisoning by paraquat herbicide is a major medical problem in parts of Asia while sporadic cases occur elsewhere. The very high case fatality of paraquat is due to inherent toxicity and lack of effective treatments. We conducted a systematic search for human studies that report toxicokinetics, mechanisms, clinical features, prognosis and treatment. Paraquat is rapidly but incompletely absorbed and then largely eliminated unchanged in urine within 12-24 h. Clinical features are largely due to intracellular effects. Paraquat generates reactive oxygen species which cause cellular damage via lipid peroxidation, activation of NF-κB, mitochondrial damage and apoptosis in many organs. Kinetics of distribution into these target tissues can be described by a two-compartment model. Paraquat is actively taken up against a concentration gradient into lung tissue leading to pneumonitis and lung fibrosis. Paraquat also causes renal and liver injury. Plasma paraquat concentrations, urine and plasma dithionite tests and clinical features provide a good guide to prognosis. Activated charcoal and Fuller's earth are routinely given to minimize further absorption. Gastric lavage should not be performed. Elimination methods such as haemodialysis and haemoperfusion are unlikely to change the clinical course. Immunosuppression with dexamethasone, cyclophosphamide and methylprednisolone is widely practised, but evidence for efficacy is very weak. Antioxidants such as acetylcysteine and salicylate might be beneficial through free radical scavenging, anti-inflammatory and NF-κB inhibitory actions. However, there are no published human trials. The case fatality is very high in all centres despite large variations in treatment.
百草枯中毒是亚洲部分地区的一个主要医学问题，而其他地方则偶有发生。百草枯的极高病死率归因于其固有毒性和缺乏有效治疗方法。我们进行了系统检索，以寻找报告毒物动力学、机制、临床特征、预后和治疗的人体研究。百草枯被迅速但不完全吸收，然后在 12-24 小时内主要以原形从尿液中排出。临床特征主要是由于细胞内效应。百草枯产生活性氧，通过脂质过氧化、NF-κB 激活、线粒体损伤和细胞凋亡，在许多器官中引起细胞损伤。分布到这些靶组织的动力学可以用双室模型来描述。百草枯主动逆浓度梯度进入肺组织，导致肺炎和肺纤维化。百草枯还会导致肾和肝损伤。血浆百草枯浓度、尿和血浆连二亚硫酸盐试验以及临床特征为预后提供了很好的指导。活性炭和 fuller's earth 通常被给予以尽量减少进一步吸收。不应进行洗胃。透析和血液灌流等清除方法不太可能改变临床病程。地塞米松、环磷酰胺和甲基强的松龙的免疫抑制作用被广泛应用，但疗效证据非常薄弱。乙酰半胱氨酸和水杨酸盐等抗氧化剂可能通过自由基清除、抗炎和 NF-κB 抑制作用而有益。然而，目前尚无人体试验的报道。尽管治疗方法存在很大差异，但所有中心的病死率都非常高。
